Previous studies of pulmonary diffusing capacity in children differed greatly in methodologies; numbers of subjects evaluated, and were performed prior to the latest ATS/ERS guidelines. The purpose of our study was to establish reference ranges for the diffusing capacity to carbon monoxide (DLCO) and alveolar volume (VA) in healthy Caucasian children using current international guidelines and contemporary equipment. Healthy children from the United States (N = 303) and from Australia (N = 176) performed acceptable measurements of single breath pulmonary diffusing capacity and alveolar volume according to current ATS/ERS guidelines. The natural log of DLCO and V-A were associated with height, age and an age-sex interaction term, while DLCO/V-A was related to height and the age-sex interaction term only. Adjustment of DLCO for hemoglobin (n = 303; USA data only) resulted is a small but significant decrease in DLCO of similar to 1% but did not significantly alter the regression equations. In this dataset there was no influence of center for DLCO or DLCO/VA, while Australian children had a statistically smaller V-A (mean difference 0.14 L after accounting for height, age and age-sex; P = 0.012). We report that diffusing capacity outcomes can be collated from multiple centers using similar equipment and collection protocols. Using collated data we have derived regression equations for pulmonary diffusing capacity outcomes in healthy Caucasian children aged 5-19 years. Pediatr Pulmonol. 2012; 47: 469-475. (C) 2011 Wiley Periodicals, Inc.

The position of division director is constantly evolving and today it has become arguably one of the most demanding positions within an academic Department of Pediatrics, requiring many of the skills and attributes of the department chair.1Fiser R.H. Daeschner C.W. Stapleton F.B. Chesney R.W. Academic missions of division chiefs in pediatric departments, parts I-4.Am J Dis Child. 1990; 144: 889-897PubMed Google Scholar, 2Cheng T.L. Szilagyi P.G. Association of Medical School Pediatric Department Chairs Leadership in academic general pediatrics.J Pediatr. 2007; 150 (452.e1): 451-452Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 3Schidlow D.V. Musings on the nature of academic medical leadership.Physician Executive. 2007; 33: 32-34PubMed Google Scholar, 4Detsky A.S. How to be a good academic leader.J Gen Intern Med. 2010; 26: 88-90Crossref PubMed Scopus (32) Google Scholar Edward Miller, MD, former Dean and Chief Executive Officer at Johns Hopkins, reflected on the qualities and skills he looked for when recruiting a department chairperson for Johns Hopkins Medicine.5Miller ED. Heads with many hats: for today's department leaders, the needed skill set is daunting. Hopkins Med 2008, spring/summer. Available from: http://www.hopkinsmedicine.org/hmn/s08/opinions2.cfm. Accessed: October 12, 2012.Google Scholar His list included people skills, financial management skills, ability to get the most out of faculty, accountability for faculty performance, humility, and openness to new ways of thinking as key characteristics for the next generation of academic program leaders. It would seem that these attributes are the skills required of a successful division director as well.5Miller ED. Heads with many hats: for today's department leaders, the needed skill set is daunting. Hopkins Med 2008, spring/summer. Available from: http://www.hopkinsmedicine.org/hmn/s08/opinions2.cfm. Accessed: October 12, 2012.Google ScholarAlthough some previous articles, including those referenced above, have reviewed the leadership skills of the academic division director for pediatric, medical, and surgical services, we were unable to find any works specifically identifying the attributes and expectations of the modern division director. Collectively, we have decades of experience leading major academic programs at leading medical centers, and have been challenged by the process of recruiting leaders for key divisions (G.L. and G.D.). This experience prompted us to define more clearly the roles and responsibilities of our division directors. What follows is a proposed “job description” for the modern division director that a Department of Pediatrics chair may use to help guide expectations during the recruiting process. Ultimately, the actual responsibilities will be influenced by the organizational structure of the department, school of medicine, and hospital, as well as by the available compensation for administrative time, division size, and internal organization.Division Director: Job Description and ExpectationsThe division director is appointed by and serves at the pleasure of the chair of the Department of Pediatrics. In certain settings, approval by the hospital's administrative structure also is required. The primary responsibilities of the division director are to provide administrative and financial leadership and to define and implement the educational, research/scholarly, and clinical service missions of the division and department. The specific roles and responsibilities of this position include, at minimum, the following components:Leadership skills•Create a positive work environment for the division.•Serve as a role model for effective communication.•Establish an environment that encourages communication at all levels within the division.•Establish a system for ensuring that information is transmitted in a timely manner to all faculty and staff.•Understand the local and national forces shaping healthcare in the US and how these forces may influence the future of the discipline.•Identify opportunities for growth of the division's clinical, research, and educational programs.•Develop division-specific research, educational, and clinical missions and monitor the division's progress in achieving these missions.•Develop programs that connect the division's faculty and fellows to community health–related services, including school-based clinics, mobile health clinics, and medical homes.Academic•Recruit new faculty and staff to fulfill the division's mission and responsibilities.•Develop a strategy to retain and develop the academic skills of existing faculty.•Develop an individual faculty development plan for each faculty member of the division that outlines goals and expectations (clinical, research, and education).•Conduct an annual performance review with each division faculty member, including written feedback regarding expectations/goals from the individual faculty development plan.•Develop a similar process for all trainees in the division consistent with Accreditation Council for Graduate Medical Education training requirements.•Understand the specifics and subtleties of the promotion process of the institution to be able to counsel junior faculty through the intricacies of promotion.•Identify appropriate mentors for junior faculty in the division in the areas of research, education, and clinical function of the division/department.•Monitor the academic progress of divisional faculty and fellows.Financial•Develop a “zero-deficit” or “surplus” divisional budget approved by the department chair.•Monitor the financial status of the division on an ongoing basis and develop corrective action plans to address deficit situations.•Evaluate and establish clinical productivity standards for all clinical faculty and staff in the division.•Compare division and faculty productivity to appropriate benchmarks and formulate plans to maximize clinical productivity as appropriate.•Ensure divisional faculty compliance with clinical practice billing and documentation rules and regulations.Administration•Submit to the chair an annual report on the division. This report should summarize the division activities in the area of research, education, and patient care, as well as notable awards and accomplishments of divisional faculty and staff.•Conduct regular meetings with all division personnel (clinical and administrative).•Conduct regular division meetings on a schedule that maximizes attendance. Minutes of these meetings should be recorded and distributed for group approval.•Participate in healthcare system, hospital, medical school, or department committees as requested or appropriate.•Lead and participate in quality assurance and performance improvement activities for the division, department, and hospital.Clinical•Oversee the delivery of clinical care provided throughout the division and ensure that the quality of care delivered meets accepted standards.•Ensure that patient access is maximized for the division.•Ensure the maintenance of on-call and ambulatory schedules.•Ensure that the divisional faculty and staff maintain positive working relationships and contact with referring physicians.•Ensure compliance with appropriate medical record documentation and timely and accurate submission of charges for clinical services by all faculty.•Ensure compliance with all internal policies and procedures promulgated by the university, medical college, department, hospital, and external regulatory agencies.Educational•Coordinate at least one annual grand rounds for the division.•Participate when requested by the chief residents in departmental teaching conferences for residents and medical students.•Ensure that division faculty are similarly responsive to these requests.•Regularly attend weekly grand rounds and departmental conferences (expectation is attendance at a minimum of 50% of these conferences).•Participate in resident and medical student education and ensure divisional faculty participation and compliance with Accreditation Council for Graduate Medical Education and Liaison Committeeon Medical Education training requirements, to ensure successful program continuation.Research•Develop a creative divisional research plan integrating clinical, translational, basic science, and health services research opportunities.•Recruit faculty whose talents and research interests are consistent with the overall divisional/departmental research program.•Encourage cross-divisional and departmental research and training collaborations•Maximize utilization of divisional research space and resources.•Monitor progress of divisional investigators.•Develop a plan to deal with gaps in research funding for investigators, as well as a plan for shortfalls in research funding for funded investigators.Departmental responsibilities•Regularly attend departmental divisional director and faculty meetings.•Communicate appropriate information from the department, medical school, and hospital to division personnel in a timely and regular manner.•Interact with and respond to requests from administrative departments (eg, marketing, finance) in a timely manner.•Actively participate in departmental fundraising activities.•Advocate for staff and patients of the division.•Address complaints regarding the division with the department chair.•Other duties as may be required for the division or department and assigned by the chair or dean. The position of division director is constantly evolving and today it has become arguably one of the most demanding positions within an academic Department of Pediatrics, requiring many of the skills and attributes of the department chair.1Fiser R.H. Daeschner C.W. Stapleton F.B. Chesney R.W. Academic missions of division chiefs in pediatric departments, parts I-4.Am J Dis Child. 1990; 144: 889-897PubMed Google Scholar, 2Cheng T.L. Szilagyi P.G. Association of Medical School Pediatric Department Chairs Leadership in academic general pediatrics.J Pediatr. 2007; 150 (452.e1): 451-452Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar, 3Schidlow D.V. Musings on the nature of academic medical leadership.Physician Executive. 2007; 33: 32-34PubMed Google Scholar, 4Detsky A.S. How to be a good academic leader.J Gen Intern Med. 2010; 26: 88-90Crossref PubMed Scopus (32) Google Scholar Edward Miller, MD, former Dean and Chief Executive Officer at Johns Hopkins, reflected on the qualities and skills he looked for when recruiting a department chairperson for Johns Hopkins Medicine.5Miller ED. Heads with many hats: for today's department leaders, the needed skill set is daunting. Hopkins Med 2008, spring/summer. Available from: http://www.hopkinsmedicine.org/hmn/s08/opinions2.cfm. Accessed: October 12, 2012.Google Scholar His list included people skills, financial management skills, ability to get the most out of faculty, accountability for faculty performance, humility, and openness to new ways of thinking as key characteristics for the next generation of academic program leaders. It would seem that these attributes are the skills required of a successful division director as well.5Miller ED. Heads with many hats: for today's department leaders, the needed skill set is daunting. Hopkins Med 2008, spring/summer. Available from: http://www.hopkinsmedicine.org/hmn/s08/opinions2.cfm. Accessed: October 12, 2012.Google Scholar Although some previous articles, including those referenced above, have reviewed the leadership skills of the academic division director for pediatric, medical, and surgical services, we were unable to find any works specifically identifying the attributes and expectations of the modern division director. Collectively, we have decades of experience leading major academic programs at leading medical centers, and have been challenged by the process of recruiting leaders for key divisions (G.L. and G.D.). This experience prompted us to define more clearly the roles and responsibilities of our division directors. What follows is a proposed “job description” for the modern division director that a Department of Pediatrics chair may use to help guide expectations during the recruiting process. Ultimately, the actual responsibilities will be influenced by the organizational structure of the department, school of medicine, and hospital, as well as by the available compensation for administrative time, division size, and internal organization. Division Director: Job Description and ExpectationsThe division director is appointed by and serves at the pleasure of the chair of the Department of Pediatrics. In certain settings, approval by the hospital's administrative structure also is required. The primary responsibilities of the division director are to provide administrative and financial leadership and to define and implement the educational, research/scholarly, and clinical service missions of the division and department. The specific roles and responsibilities of this position include, at minimum, the following components:Leadership skills•Create a positive work environment for the division.•Serve as a role model for effective communication.•Establish an environment that encourages communication at all levels within the division.•Establish a system for ensuring that information is transmitted in a timely manner to all faculty and staff.•Understand the local and national forces shaping healthcare in the US and how these forces may influence the future of the discipline.•Identify opportunities for growth of the division's clinical, research, and educational programs.•Develop division-specific research, educational, and clinical missions and monitor the division's progress in achieving these missions.•Develop programs that connect the division's faculty and fellows to community health–related services, including school-based clinics, mobile health clinics, and medical homes.Academic•Recruit new faculty and staff to fulfill the division's mission and responsibilities.•Develop a strategy to retain and develop the academic skills of existing faculty.•Develop an individual faculty development plan for each faculty member of the division that outlines goals and expectations (clinical, research, and education).•Conduct an annual performance review with each division faculty member, including written feedback regarding expectations/goals from the individual faculty development plan.•Develop a similar process for all trainees in the division consistent with Accreditation Council for Graduate Medical Education training requirements.•Understand the specifics and subtleties of the promotion process of the institution to be able to counsel junior faculty through the intricacies of promotion.•Identify appropriate mentors for junior faculty in the division in the areas of research, education, and clinical function of the division/department.•Monitor the academic progress of divisional faculty and fellows.Financial•Develop a “zero-deficit” or “surplus” divisional budget approved by the department chair.•Monitor the financial status of the division on an ongoing basis and develop corrective action plans to address deficit situations.•Evaluate and establish clinical productivity standards for all clinical faculty and staff in the division.•Compare division and faculty productivity to appropriate benchmarks and formulate plans to maximize clinical productivity as appropriate.•Ensure divisional faculty compliance with clinical practice billing and documentation rules and regulations.Administration•Submit to the chair an annual report on the division. This report should summarize the division activities in the area of research, education, and patient care, as well as notable awards and accomplishments of divisional faculty and staff.•Conduct regular meetings with all division personnel (clinical and administrative).•Conduct regular division meetings on a schedule that maximizes attendance. Minutes of these meetings should be recorded and distributed for group approval.•Participate in healthcare system, hospital, medical school, or department committees as requested or appropriate.•Lead and participate in quality assurance and performance improvement activities for the division, department, and hospital.Clinical•Oversee the delivery of clinical care provided throughout the division and ensure that the quality of care delivered meets accepted standards.•Ensure that patient access is maximized for the division.•Ensure the maintenance of on-call and ambulatory schedules.•Ensure that the divisional faculty and staff maintain positive working relationships and contact with referring physicians.•Ensure compliance with appropriate medical record documentation and timely and accurate submission of charges for clinical services by all faculty.•Ensure compliance with all internal policies and procedures promulgated by the university, medical college, department, hospital, and external regulatory agencies.Educational•Coordinate at least one annual grand rounds for the division.•Participate when requested by the chief residents in departmental teaching conferences for residents and medical students.•Ensure that division faculty are similarly responsive to these requests.•Regularly attend weekly grand rounds and departmental conferences (expectation is attendance at a minimum of 50% of these conferences).•Participate in resident and medical student education and ensure divisional faculty participation and compliance with Accreditation Council for Graduate Medical Education and Liaison Committeeon Medical Education training requirements, to ensure successful program continuation.Research•Develop a creative divisional research plan integrating clinical, translational, basic science, and health services research opportunities.•Recruit faculty whose talents and research interests are consistent with the overall divisional/departmental research program.•Encourage cross-divisional and departmental research and training collaborations•Maximize utilization of divisional research space and resources.•Monitor progress of divisional investigators.•Develop a plan to deal with gaps in research funding for investigators, as well as a plan for shortfalls in research funding for funded investigators.Departmental responsibilities•Regularly attend departmental divisional director and faculty meetings.•Communicate appropriate information from the department, medical school, and hospital to division personnel in a timely and regular manner.•Interact with and respond to requests from administrative departments (eg, marketing, finance) in a timely manner.•Actively participate in departmental fundraising activities.•Advocate for staff and patients of the division.•Address complaints regarding the division with the department chair.•Other duties as may be required for the division or department and assigned by the chair or dean. The division director is appointed by and serves at the pleasure of the chair of the Department of Pediatrics. In certain settings, approval by the hospital's administrative structure also is required. The primary responsibilities of the division director are to provide administrative and financial leadership and to define and implement the educational, research/scholarly, and clinical service missions of the division and department. The specific roles and responsibilities of this position include, at minimum, the following components: Leadership skills•Create a positive work environment for the division.•Serve as a role model for effective communication.•Establish an environment that encourages communication at all levels within the division.•Establish a system for ensuring that information is transmitted in a timely manner to all faculty and staff.•Understand the local and national forces shaping healthcare in the US and how these forces may influence the future of the discipline.•Identify opportunities for growth of the division's clinical, research, and educational programs.•Develop division-specific research, educational, and clinical missions and monitor the division's progress in achieving these missions.•Develop programs that connect the division's faculty and fellows to community health–related services, including school-based clinics, mobile health clinics, and medical homes. •Create a positive work environment for the division.•Serve as a role model for effective communication.•Establish an environment that encourages communication at all levels within the division.•Establish a system for ensuring that information is transmitted in a timely manner to all faculty and staff.•Understand the local and national forces shaping healthcare in the US and how these forces may influence the future of the discipline.•Identify opportunities for growth of the division's clinical, research, and educational programs.•Develop division-specific research, educational, and clinical missions and monitor the division's progress in achieving these missions.•Develop programs that connect the division's faculty and fellows to community health–related services, including school-based clinics, mobile health clinics, and medical homes. Academic•Recruit new faculty and staff to fulfill the division's mission and responsibilities.•Develop a strategy to retain and develop the academic skills of existing faculty.•Develop an individual faculty development plan for each faculty member of the division that outlines goals and expectations (clinical, research, and education).•Conduct an annual performance review with each division faculty member, including written feedback regarding expectations/goals from the individual faculty development plan.•Develop a similar process for all trainees in the division consistent with Accreditation Council for Graduate Medical Education training requirements.•Understand the specifics and subtleties of the promotion process of the institution to be able to counsel junior faculty through the intricacies of promotion.•Identify appropriate mentors for junior faculty in the division in the areas of research, education, and clinical function of the division/department.•Monitor the academic progress of divisional faculty and fellows. •Recruit new faculty and staff to fulfill the division's mission and responsibilities.•Develop a strategy to retain and develop the academic skills of existing faculty.•Develop an individual faculty development plan for each faculty member of the division that outlines goals and expectations (clinical, research, and education).•Conduct an annual performance review with each division faculty member, including written feedback regarding expectations/goals from the individual faculty development plan.•Develop a similar process for all trainees in the division consistent with Accreditation Council for Graduate Medical Education training requirements.•Understand the specifics and subtleties of the promotion process of the institution to be able to counsel junior faculty through the intricacies of promotion.•Identify appropriate mentors for junior faculty in the division in the areas of research, education, and clinical function of the division/department.•Monitor the academic progress of divisional faculty and fellows. Financial•Develop a “zero-deficit” or “surplus” divisional budget approved by the department chair.•Monitor the financial status of the division on an ongoing basis and develop corrective action plans to address deficit situations.•Evaluate and establish clinical productivity standards for all clinical faculty and staff in the division.•Compare division and faculty productivity to appropriate benchmarks and formulate plans to maximize clinical productivity as appropriate.•Ensure divisional faculty compliance with clinical practice billing and documentation rules and regulations. •Develop a “zero-deficit” or “surplus” divisional budget approved by the department chair.•Monitor the financial status of the division on an ongoing basis and develop corrective action plans to address deficit situations.•Evaluate and establish clinical productivity standards for all clinical faculty and staff in the division.•Compare division and faculty productivity to appropriate benchmarks and formulate plans to maximize clinical productivity as appropriate.•Ensure divisional faculty compliance with clinical practice billing and documentation rules and regulations. Administration•Submit to the chair an annual report on the division. This report should summarize the division activities in the area of research, education, and patient care, as well as notable awards and accomplishments of divisional faculty and staff.•Conduct regular meetings with all division personnel (clinical and administrative).•Conduct regular division meetings on a schedule that maximizes attendance. Minutes of these meetings should be recorded and distributed for group approval.•Participate in healthcare system, hospital, medical school, or department committees as requested or appropriate.•Lead and participate in quality assurance and performance improvement activities for the division, department, and hospital. •Submit to the chair an annual report on the division. This report should summarize the division activities in the area of research, education, and patient care, as well as notable awards and accomplishments of divisional faculty and staff.•Conduct regular meetings with all division personnel (clinical and administrative).•Conduct regular division meetings on a schedule that maximizes attendance. Minutes of these meetings should be recorded and distributed for group approval.•Participate in healthcare system, hospital, medical school, or department committees as requested or appropriate.•Lead and participate in quality assurance and performance improvement activities for the division, department, and hospital. Clinical•Oversee the delivery of clinical care provided throughout the division and ensure that the quality of care delivered meets accepted standards.•Ensure that patient access is maximized for the division.•Ensure the maintenance of on-call and ambulatory schedules.•Ensure that the divisional faculty and staff maintain positive working relationships and contact with referring physicians.•Ensure compliance with appropriate medical record documentation and timely and accurate submission of charges for clinical services by all faculty.•Ensure compliance with all internal policies and procedures promulgated by the university, medical college, department, hospital, and external regulatory agencies. •Oversee the delivery of clinical care provided throughout the division and ensure that the quality of care delivered meets accepted standards.•Ensure that patient access is maximized for the division.•Ensure the maintenance of on-call and ambulatory schedules.•Ensure that the divisional faculty and staff maintain positive working relationships and contact with referring physicians.•Ensure compliance with appropriate medical record documentation and timely and accurate submission of charges for clinical services by all faculty.•Ensure compliance with all internal policies and procedures promulgated by the university, medical college, department, hospital, and external regulatory agencies. Educational•Coordinate at least one annual grand rounds for the division.•Participate when requested by the chief residents in departmental teaching conferences for residents and medical students.•Ensure that division faculty are similarly responsive to these requests.•Regularly attend weekly grand rounds and departmental conferences (expectation is attendance at a minimum of 50% of these conferences).•Participate in resident and medical student education and ensure divisional faculty participation and compliance with Accreditation Council for Graduate Medical Education and Liaison Committeeon Medical Education training requirements, to ensure successful program continuation. •Coordinate at least one annual grand rounds for the division.•Participate when requested by the chief residents in departmental teaching conferences for residents and medical students.•Ensure that division faculty are similarly responsive to these requests.•Regularly attend weekly grand rounds and departmental conferences (expectation is attendance at a minimum of 50% of these conferences).•Participate in resident and medical student education and ensure divisional faculty participation and compliance with Accreditation Council for Graduate Medical Education and Liaison Committeeon Medical Education training requirements, to ensure successful program continuation. Research•Develop a creative divisional research plan integrating clinical, translational, basic science, and health services research opportunities.•Recruit faculty whose talents and research interests are consistent with the overall divisional/departmental research program.•Encourage cross-divisional and departmental research and training collaborations•Maximize utilization of divisional research space and resources.•Monitor progress of divisional investigators.•Develop a plan to deal with gaps in research funding for investigators, as well as a plan for shortfalls in research funding for funded investigators. •Develop a creative divisional research plan integrating clinical, translational, basic science, and health services research opportunities.•Recruit faculty whose talents and research interests are consistent with the overall divisional/departmental research program.•Encourage cross-divisional and departmental research and training collaborations•Maximize utilization of divisional research space and resources.•Monitor progress of divisional investigators.•Develop a plan to deal with gaps in research funding for investigators, as well as a plan for shortfalls in research funding for funded investigators. Departmental responsibilities•Regularly attend departmental divisional director and faculty meetings.•Communicate appropriate information from the department, medical school, and hospital to division personnel in a timely and regular manner.•Interact with and respond to requests from administrative departments (eg, marketing, finance) in a timely manner.•Actively participate in departmental fundraising activities.•Advocate for staff and patients of the division.•Address complaints regarding the division with the department chair.•Other duties as may be required for the division or department and assigned by the chair or dean. •Regularly attend departmental divisional director and faculty meetings.•Communicate appropriate information from the department, medical school, and hospital to division personnel in a timely and regular manner.•Interact with and respond to requests from administrative departments (eg, marketing, finance) in a timely manner.•Actively participate in departmental fundraising activities.•Advocate for staff and patients of the division.•Address complaints regarding the division with the department chair.•Other duties as may be required for the division or department and assigned by the chair or dean.

BACKGROUND:Catheter-associated bloodstream infections have been reported to occur in 3% to 8% of all central venous catheters inserted and are the predominant cause of hospital-acquired infection in intensive care units.OBJECTIVE:Decreasing the pediatric intensive care unit rate of catheter-associated bloodstream infections became a high priority in 2008 for all members of the intensive care unit team affiliated with central venous catheter insertion and maintenance.INTERVENTIONS:Through a series of multidisciplinary initiatives, the annual average catheter-associated bloodstream infection rate in the pediatric intensive care unit fell from 7.9 infections per 1000 central catheter days in 2007 to 1.3 infections per 1000 central catheter days in 2009, a decrease of 83%. We attribute this success to the implementation of several key interventions, adherence to published insertion and maintenance bundles, and collaboration among pediatric intensive care unit physicians and nurses in all aspects of central catheter care.MEASUREMENTS AND MAIN RESULTS:Statistically significant interventions included improvements to central venous catheter insertion practices, the development of a dedicated central catheter team, and regular collaborative discussion of central venous catheter necessity. In this 24-month period, this equates to 50 catheter-associated infections avoided, six potential deaths prevented, and an estimated cost savings of $1.45 million (based on $29,000 per infection).CONCLUSION:While implementation of these and other interventions has shown a positive impact, this project will continue into the future to assure sustainable successes and continued best practice improvements.

We previously demonstrated a very high prevalence of wheezing (89%) and lower pulmonary function tests (PFT) in rural Honduran children of the Rio Grande O Choluteca valley where sugar cane is burned 8 months of the year compared to children of Jamastran valley (17% wheezing) where no crops are burned. We applied a similar asthma/allergy questionnaire and performed PFT on sugar cane field workers (SC) of the Rio Grande O Choluteca valley and tobacco field workers (TOB) of the Jamastran valley. Tables 1 & 2 summarize questionnaire findings and PFT values of the two groups. We found the SC workers to be significantly younger with thus fewer years working in the fields compared to the TOB workers. Both groups were found to have similarly high prevalence9s of ever wheezed, wheezed in last 12 months, night cough, smoking frequency, chronic rhinitis and conjunctivitis. SC workers have significantly lower FVC and FEV-1. We conclude that both SC and TOB field workers in Honduras have a high prevalence of asthma and allergy symptoms and SC workers, although younger with fewer years of exposure, have lower pulmonary function. Individual air quality sampling of the two groups is needed to delineate the contribution of environmental work exposure to these findings.

After completing this article, readers should be able to: A 16-year-old girl who has no significant previous medical history presents to the emergency department with a 4-day history of nausea, vomiting, fever, chills, diarrhea, leg cramps, abdominal pain, and headaches. She is finishing her menstrual period and arrives with a tampon in place, which she reports that she inserted yesterday. Her vital signs include a heart rate of 165 beats/min, respiratory rate of 28 breaths/min, blood pressure 65/30 mm Hg, and oxygen saturation of 100% on 4 L/min of oxygen. The most likely diagnosis for this patient is toxic shock syndrome, which was later confirmed with a positive antibody test.The initial arterial blood gas (ABG) values are:Such findings are suggestive of metabolic acidosis with respiratory compensation.Further laboratory results are:The apparently normal AG is misleading. After correcting the AG for hypoalbuminemia, the adjusted AG is 17 mEq/L (17 mmol/L).Lactic acidemia due to shock, one of the likely causes for increased AG metabolic acidosis, is confirmed by a high serum lactate value of 6.9 mg/dL (0.8 mmol/L). One hour later, the ABG values are:This ABG panel reveals metabolic acidosis without respiratory compensation due to developing respiratory failure.The loss of acid-base balance is an expression of various conditions encountered frequently in clinical practice. Changes in hydrogen ion concentration can lead to unraveling of the protein tertiary structure, thereby causing enzyme dysfunction, enzyme loss, and cell death. Understanding the physiology behind various disturbances in acid-base balance is necessary for determining a correct diagnosis and management plan. Maintaining acid-base homeostasis involves the lungs, kidneys, and a very complex system of buffers, all aiming to maintain the normal pH (7.35 to 7.45) of the arterial blood. Lowering the arterial pH below 7.35 is termed acidosis, and an increase of the arterial pH above 7.45 constitutes alkalosis.Metabolic acidosis is associated with a low pH and low HCO3− concentration. Metabolic alkalosis is associated with a high pH and high HCO3− concentration. Respiratory acidosis is associated with a low pH and high Pco2. Respiratory alkalosis is associated with a high pH and low Pco2 (Fig. 1).Each acid-base disorder leads to countering respiratory or renal compensatory responses that attempt to normalize the pH. In metabolic acidosis, for example, ventilation is increased, resulting in a decrease in Pco2, which tends to raise the pH toward normal. These compensatory attempts never overshoot correcting the pH (Figs. 2 and 3). The process of acid-base regulation involves the respiratory system (controls Pco2), kidneys (regulates plasma HCO3− by changes in acid excretion), and a very complex system of extracellular and intracellular buffers.The respiratory system contributes to acid-base balance via timely adjustments in alveolar minute ventilation that maintain systemic acid-base equilibrium in response to alterations in systemic pH and arterial Pco2. Systemic pH is monitored by central chemoreceptors on the ventrolateral surface of the medulla oblongata and arterial Pco2 (as well as arterial Po2) by peripheral chemoreceptors located at the carotid and aortic bodies. These chemoreceptors act through central respiratory control centers in the pons and medulla to coordinate the respiratory muscle efforts of inhalation and exhalation, leading to adjustments in both components of minute ventilation: tidal volume and respiratory cycle frequency. Lung-mediated changes in arterial Pco2 can lead to rapid alteration in systemic hydrogen ions (H+) because CO2 is lipid-soluble and may readily cross cell membranes according to the following equation: H+ + HCO3−↔H2CO3 (carbonic acid)↔CO2 + H2O (water). Under normal physiologic conditions, this process allows for tight control of arterial Pco2 near 40 mm Hg.The kidney's role in acid-base balance consists of reabsorbing filtered HCO3− and excreting the daily acid load derived principally from the metabolism of sulfur-containing amino acids. Ninety percent of filtered HCO3− is reabsorbed in the proximal tubules, primarily by Na+-H+ exchange, and the remaining 10% is reabsorbed in the distal nephron, primarily via hydrogen secretion by a proton pump (H+-ATPase). Under normal conditions, no HCO3− is present in the final urine. The excretion of the daily H+ load occurs in the distal tubule. Once excreted in the urine, the H+ must be bound to a buffer to avoid excessive urine acidification and promote further excretion. The two primary buffers in the urine are ammonia (NH3), which is excreted and measured as ammonium (NH4+) and phosphate (referred to and measured as titratable acidity). The kidneys synthesize and excrete NH3, which combines with H+ excreted by the collecting duct cells to form NH4+: H++NH3=NH4+. NH3 diffuses freely across membranes; NH4+does not. Failure to produce and excrete sufficient NH4+, therefore, leads to the development of metabolic acidosis.The most important buffer in the extracellular fluid is HCO3−, due both to its relatively high concentration and its ability to vary Pco2 via changes in alveolar ventilation. Chemoreceptor analysis of arterial pH and Pco2 allows for centrally mediated adjustments in minute ventilation to maintain arterial Pco2. The HCO3− interacts with H+, as demonstrated in the following formula: H+ + HCO3− ↔H2CO3↔CO2 + H2O. This reaction serves as the basis for the Henderson-Hasselbalch equation: pH=6.1 + log (HCO3−/0.03 × Pco2). Although this equation describes a patient's acid-base status, it does not provide insight into the mechanism of the acid-base disorder. The Henderson-Hasselbalch equation lists Pco2 and HCO3− as independent predictors of acid-base balance, but in reality they are interdependent (as suggested by the chemical reaction H+ + HCO3− described previously). Furthermore, the Henderson-Hasselbalch equation does not account for other important nonbicarbonate buffers present in the body, such as the primary intracellular buffers of proteins, organic and inorganic phosphates, and hemoglobin. In addition, bone is an important site for buffering of acid and base loads.Acid-base balance is assessed by blood gas analysis and serum measurement of several important electrolytes, leading to the calculation of the AG. Blood gas analyzers measure the pH and the Pco2 directly. The HCO3− value is calculated from the Henderson-Hasselbalch equation. The BE value also is calculated as the amount of base/acid that should be added to a sample of whole blood in vitro to restore the pH to 7.40 while the Pco2 is held at 40 mm Hg. The Pco2 not only points to the type of disorder (respiratory or metabolic) but also corresponds to the magnitude of the disorder. The AG method was developed to include other nonbicarbonate buffers in the analysis. Based on the principle of electroneutrality, the sum of the positive charges should equal the sum of the negative charges as follows: Na++K++Mg2+ (magnesium) +Ca2+ (calcium) +H+=Cl−+ HCO3−+ protein −+ PO43− (phosphate)+ OH−+ SO42− (sulfate)+ CO32−+ conjugate base−. Sodium, chloride, and HCO3− are measured easily in the serum. Therefore, the AG is calculated by the formula AG={Na+} − {Cl−+ HCO3−}. A normal AG is 12±2 mEq/L (12 mmol/L). Some clinicians and some published reports include potassium as a measured cation in the calculation of AG, which raises the normal value by 4 mEq/L (4 mmol/L).The AG is defined as the difference between the unmeasured plasma anions and the unmeasured plasma cations. Clinically, an elevated AG is believed to reflect an increase of unmeasured anions and, therefore, a metabolic acidosis. This concept is explained by the fact that unmeasured cations (Mg2+ + Ca2+ + H+) are more tightly controlled and the unmeasured anions have a greater tendency to fluctuate. Theoretically, the AG also can increase following a decrease in serum K+, Ca2+, or Mg2+, but the normal concentration of these cations is so low that a reduction does not have a significant clinical impact on the AG.In general, these principles hold true for the previously healthy individual who develops an acute illness. However, for the critically ill host whose plasma protein concentrations are greatly reduced, the low protein values hide an associated increase in unmeasured anions. Without the correction for hypoalbuminemia, it is possible to overlook a true high AG acidosis, mistakenly assuming it to be a normal AG acidosis.According to the Figge formula, each 1-g/dL reduction in the serum albumin concentration is expected to reduce the AG by 2.5 mEq/L: Metabolic acidosis is defined as an acid-base imbalance that leads to anion excess (low HCO3− concentration) and subsequently to an arterial pH below 7.35. Several mechanisms can lead to metabolic acidosis: excess acid production, increased acid intake, decreased renal acid excretion, increased HCO3− loss from the gastrointestinal (GI) tract, and excess HCO3− excretion in the kidney. For a patient who has intact respiratory function, developing metabolic acidosis leads to respiratory compensation by hyperventilation. Each 1-mEq/L reduction in plasma HCO3− concentration prompts a 1.2-mm Hg compensatory fall in the Pco2. Clinically, the patient's respiratory rate increases within the first hour of the onset of metabolic acidosis, and respiratory compensation is achieved within 24 hours. Failure of the respiratory system to compensate for metabolic acidosis is an ominous sign that should trigger careful evaluation of the patient's mental status and cardiorespiratory function.Calculating the AG is a very useful initial step in diagnosing various causes of metabolic acidosis.Metabolic acidosis with normal AG reflects an imbalance of the measured plasma anions and cations. According to the formula: AG=Na+ − (Cl− + HCO3−), metabolic acidosis with normal AG can be explained by excessive loss of HCO3− (in the stool or in the urine) or by inability to excrete hydrogen ions. Table 1lists the most frequent conditions leading to normal AG metabolic acidosis.Of particular note is renal tubular acidosis (RTA), a complex set of disorders of the kidney that can lead to normal AG metabolic acidosis. One disorder is the inability to excrete the daily acid load (type 1 RTA), leading to progressive H+ ion retention and low plasma HCO3− concentration (<10 mEq/L [10 mmol/L]). Another disorder arises from the inability to reabsorb HCO3− normally in the proximal tubule (proximal RTA or type 2 RTA). HCO3− is lost in the urine despite some reabsorption in the distal nephron, leading to metabolic acidosis and alkaline urine.Normal AG metabolic acidosis caused by excessive HCO3− losses may be corrected by slow infusion of sodium bicarbonate-containing intravenous fluids.Elevated AG metabolic acidosis results from an excess of unmeasured anions. Various conditions that cause an accumulation of unmeasured anions, leading to high AG metabolic acidosis, are listed in Table 2.When faced with an elevated AG metabolic acidosis, calculating the osmotic gap may help determine the underlying condition. Similar to the AG, the osmotic gap is the difference between the measured serum osmolality and the calculated value. The calculated serum osmolality is: 2 × [Na+] + glucose/18 + BUN/2.8. A normal osmotic gap should be 12±2 mOsm/L. A high osmotic gap is a sign of an excess of an unmeasured osmotic active substance such as ethylene glycol (antifreeze), methanol (wood alcohol), or paraldehyde.Ketoacidosis describes accumulation of ketone bodies (beta-hydroxybutyrate and acetoacetic acid) following excessive intracellular use of lipids as a metabolic substrate. This metabolic shift occurs during starvation or fasting or as a reflection of a lack of appropriate metabolic substrate for energy production (during specific diets where carbohydrates are replaced with lipids). Hyperketotic diets sometimes are employed for intractable epilepsy in an effort to decrease the seizure threshold. Diabetic ketoacidosis (DKA) results from a decrease in insulin production that leads to an inability to transport glucose into the cell. The cell shifts to lipid metabolism, despite the surrounding hyperglycemia (also described as “starvation in the middle of the plenty”). The diagnosis of DKA is confirmed by the findings of hyperglycemia, a high AG acidosis, ketonuria, and ketonemia. The earliest symptoms of DKA are related to hyperglycemia. Older children and adolescents typically present with polyuria (due to the glucose-induced osmotic diuresis), polydipsia (due to the increased urinary losses), fatigue, and weight loss. Hypovolemia may be severe if urinary losses are not replaced, with the presentation of very dry mucous membranes and prolonged capillary refill time. As a result of worsening metabolic acidosis, the patient develops hyperventilation and deep (Kussmaul) respirations, representing respiratory compensation for metabolic acidosis. Hyperpnea develops from an increase in minute volume (rate × tidal volume) or from increased tidal volume alone without an increase in respiratory rate. When DKA is being managed, the patient's chest excursion and respiratory rate should be observed carefully to determine if hyperpnea is present. In infants, hyperpnea may be manifested only by tachypnea.Without prompt medical attention, DKA can progress to cerebral edema and cardiorespiratory arrest. Neurologic findings, ranging from drowsiness, lethargy, and obtundation to coma, are related to the severity of hyperosmolality or to the degree of acidosis. Treatment of DKA includes sensitive correction of the underlying insulin, volume, and electrolyte deficiencies.Lactic acidosis, another cause of an elevated AG, occurs when cells shift to anaerobic pathways for energy production as a result of tissue hypoxia due to inappropriate tissue perfusion, inappropriate oxygen supply, or mitochondrial dysfunction (as seen in inborn errors of metabolism or ingestion of drugs or toxins). The clinical presentation may involve seizures or symptoms consistent with the initial disorder that led to lactic acidosis, such as cyanosis, signs and symptoms suggestive of tissue hypoperfusion, and hypotension. As lactic acidosis worsens, further hemodynamic compromise occurs. Management should be targeted to restoring adequate tissue perfusion and oxygen supply by treating the underlying cause of the lactic acidosis. Several inborn errors of metabolism can present with high AG metabolic acidosis. Based on the affected metabolic pathway, the increased AG is caused by a different chemical substance: urea cycle defects present with hyperammonemia; or inborn errors of amino acids, carbohydrate, or organic acid metabolism present either with ketoacidosis, lactic acidosis (as in Krebs cycle defects), or increased organic acids production. Symptoms often are nonspecific and include poor feeding, failure to thrive, seizures, and vomiting. Managing inborn errors of metabolism involves identifying the defective or deficient enzyme and limiting the intake of the metabolic substrate that requires the use of that particular enzyme. In selected cases, dialysis may be the appropriate tool for removing the excess anion.Ingestions of various chemical substances are another cause of metabolic acidosis with an elevated AG. Salicylate overdose is well known to cause increased AG metabolic acidosis by interfering with cellular metabolism (uncoupling of oxidative phosphorylation). Early symptoms of salicylate overdose include tinnitus, fever, vertigo, nausea, vomiting, and diarrhea. More severe intoxication can cause altered mental status, coma, noncardiac pulmonary edema, and death. Most patients show signs of intoxication when the plasma salicylate concentration exceeds 40 mg/dL. Treatment of salicylate ingestion involves promoting alkaline diuresis to enhance renal salicylate excretion. In severe cases, dialysis may be required (generally considered when plasma salicylate concentrations exceed 80 mg/dL in acute intoxication and 60 mg/dL in chronic ingestions). Toluene inhalation also can lead to metabolic acidosis with an increased AG. In patients who experience toluene ingestion (glue sniffing), the overproduced hippurate is both filtered and secreted by the kidneys, leading to rapid elimination in the urine. As a result, the AG may be near-normal or normal at the time of presentation and the patient might be diagnosed mistakenly as having a normal AG acidosis.Ethylene glycol (antifreeze), methanol, and paraldehyde ingestion lead to an increased AG metabolic acidosis and an increased osmotic gap. Both the AG and the acidosis due to methanol and ethylene glycol ingestions result from metabolism of the parent compound. Neither may be seen in patients early in the course of ingestion or when there is concurrent ingestion of ethanol. Ethanol combines competitively with alcohol dehydrogenase, thereby slowing the metabolism of methanol or ethylene glycol to their toxic metabolites and slowing the appearance of both the acidosis and the high AG. This effect explains why ethanol administration is used in the medical management of methanol and ethylene glycol ingestions, along with fomepizole (alcohol dehydrogenase inhibitor). Management of ethylene glycol and methanol toxicity also involves hemodialysis, which removes both the ingested substance and the metabolic byproducts from the serum.Massive ingestions of creams containing propylene glycol (eg, silver sulfadiazine) also can lead to increased AG metabolic acidosis.Renal failure causes an increased AG metabolic acidosis due to the failure to excrete H+. Normally, elimination of the serum acid load is achieved by urinary excretion of H+, both as titratable acidity and as NH4+. Titratable acid is a term used to describe acids such as phosphoric acid and sulfuric acid present in the urine. The term explicitly excludes NH4+ as a source of acid and is part of the calculation for net acid excretion. The term titratable acid was chosen based on the chemical reaction of titration (neutralization) of those acids in reaction with sodium hydroxide. As the number of functioning nephrons declines in chronic kidney disease and the glomerular filtration rate decreases to below 25% of normal, the patient develops progressive high AG metabolic acidosis (hyperchloremia may occur transiently in the initial phases of renal failure). In addition to the decrease in NH4+ excretion, decreased titratable acidity (primarily as phosphate) may play a role in the pathogenesis of metabolic acidosis in patients who experience advanced kidney disease. Of course, dialysis often is employed to correct the severe fluid and electrolyte imbalances generated by renal failure.Regardless of the cause, acidemia, if untreated, can lead to significant adverse consequences (Table 3).Use of HCO3− therapy to adjust the pH for patients who have metabolic acidosis is controversial. Slow infusion of sodium bicarbonate-containing intravenous fluids can be used in cases of normal AG metabolic acidosis to replenish excessive HCO3− losses (eg, as a result of excessive diarrhea). However, infusing sodium bicarbonate-containing fluids for increased AG metabolic acidosis has questionable benefit and should not be used clinically.As discussed, HCO3− combines with H+, leading to H2CO3 that subsequently dissociates to CO2 and H2O. Infusing HCO3− decreases serum pH and raises CO2 and H2O. Neither the cell membranes nor the blood-brain barrier is very permeable to HCO3−; CO2 diffuses freely to the intracellular space, where it combines with H2O, leading to H2CO3 and worsening of the intracellular pH. Administering intravenous sodium bicarbonate to a patient who has an increased AG metabolic acidosis can lead to a false sense of security because the underlying problem is hidden by an artificially improved serum pH.Sodium bicarbonate once held a prominent position in the management of cardiac arrest. Reversing the acidosis caused by global hypoperfusion made physiologic sense because severe acidemia may worsen tissue perfusion by decreasing cardiac contractility. However, the most effective means of correcting the acidosis in cardiac arrest is to restore adequate oxygenation, ventilation, and tissue perfusion. Because most pediatric cardiac arrests are due to respiratory failure, support of ventilation through early intubation is the primary treatment, followed by support of the circulation with fluids and inotropic agents. Currently, the American Heart Association recommends that sodium bicarbonate administration be considered only in children who suffer prolonged cardiac arrest and documented severe metabolic acidosis and who fail to respond to oxygenation, ventilation, intravenous fluids, and chest compressions combined with epinephrine in recommended doses.Metabolic alkalosis is defined as an acid-base imbalance leading to increased plasma HCO3− and an arterial pH above 7.45. Several mechanisms can lead to the elevation in the plasma HCO3−: excessive hydrogen loss, functional addition of new HCO3−, and volume contraction around a relatively constant amount of extracellular HCO3− (called a “contraction alkalosis”). The kidneys are extremely efficient in eliminating excess HCO3− in the urine. A confounding factor is required for serum HCO3− to accumulate, such as impaired renal function, K+ depletion, or volume depletion. In general, a patient compensates for a metabolic alkalosis by decreasing ventilation. Respiratory compensation by hypoventilation raises Pco2 by 0.7 mm Hg for every 1 mEq/L (1 mmol/L) of serum HCO3− increase.Excessive H+ losses can occur either in the urine or GI tract and lead to HCO3− accumulation as the result of the following reactions:H2O↔H++HO−HO−+CO2↔HCO3−Increased loss of gastric content, which has high concentrations of hydrogen chloride, as a result of persistent vomiting (eg, self-induced, pyloric stenosis) or high nasogastric tube drainage leads to metabolic alkalosis. If fluid losses continue unreplaced, dehydration and lactic acidosis ultimately develop. Of note, infants of mothers who have bulimia have metabolic alkalosis at birth.High H+ loss in the urine can occur in the distal nephron. Increased secretion of aldosterone stimulates the secretory H-ATPase pump, increasing Na+ reabsorption, thereby making the lumen more electronegative and causing more H+ and K+ excretion, which results in concurrent metabolic alkalosis and hypokalemia. Patients who have primary mineralocorticoid excess present with hypokalemia and hypertension. In contrast, secondary hyperaldosteronism due to congestive heart failure or cirrhosis usually does not present with metabolic alkalosis or hypokalemia because the above-mentioned mechanism is blunted by decreased distal nephron Na+ delivery. Iatrogenic metabolic alkalosis along with volume contraction can occur in patients treated with loop or thiazide diuretics, which cause Cl− depletion and increased delivery of Na+ to the collecting duct, which enhances K+ and H+ secretion.Bartter and Gitelman syndromes present with metabolic alkalosis and hypokalemia due to a genetic defect in the transporters in the loop of Henle and distal tubule, respectively, the same locations as those inhibited by loop and thiazide diuretics.In addition to H+ loss, metabolic alkalosis also can be induced by the shift of H+ into the cells.As discussed previously, hypokalemia is a frequent finding in patients who have metabolic alkalosis. Hypokalemia by itself causes intracellular acidosis and increased serum alkalosis by the following mechanism: intracellular K+ shifts into the serum to replete the extracellular stores, and to maintain electroneutrality, H+ enters the cells. Hydrogen movement into the cells lowers the intracellular pH and leaves unbuffered excess HCO3− in the serum. The intracellular acidosis in renal tubular cells promotes H+ secretion and, therefore, HCO3− reabsorption.Metabolic alkalosis due to functional addition of “new” HCO3− can occur by several mechanisms: decreased renal excretion of HCO3−, posthypercapnic alkalosis, or excessive intake or administration of alkali.Renal failure can lead to metabolic alkalosis because the kidneys fail to excrete excess HCO3−. Chronic respiratory acidosis (retention of CO2) leads to a compensatory increase in hydrogen secretion and an ensuing increase in the plasma HCO3− concentration to correct the pH. When the Pco2 is decreased rapidly by mechanical ventilation of a patient who has chronic respiratory acidosis, the ensuing metabolic alkalosis is slow to disappear. Because Cl− loss often is present in posthypercapnic alkalosis, repleting the Cl− deficit may be essential to correct the alkalosis. Furthermore, the acute fall in Pco2 in a person who has chronic respiratory acidosis raises the cerebral intracellular pH acutely, a change that can induce serious neurologic abnormalities and death because CO2 can diffuse freely across the blood-brain barrier out of the intracellular space, leading to severe alkalosis. Accordingly, the Pco2 must be reduced gradually in mechanically ventilated patients who present initially with chronic hypercapnia.Alkali administration does not induce metabolic alkalosis in healthy people because the healthy kidney can excrete HCO3− rapidly in the urine. However, metabolic alkalosis can occur if very large quantities of HCO3− are administered acutely or if the ability to excrete HCO3− is impaired. The administration of large quantities of citrate is known to lead to metabolic alkalosis. Examples of large administrations of citrate are infusion of more than 8 units of banked blood or fresh frozen plasma or administration of citrate as an anticoagulant during dialysis. Contraction alkalosis occurs when relatively large volumes of HCO3−-free fluid are lost, a situation frequently seen with administration of intravenous loop diuretics. Contraction alkalosis also may occur in other disorders in which a high-Cl−, low-HCO3− solution is lost, such as sweat losses in cystic fibrosis, loss of gastric secretions in patients who have achlorhydria, and fluid loss from frequent stooling by patients who have congenital chloridorrhea, a rare congenital secretory diarrhea. Regardless of the cause, alkalosis, if untreated, can lead to significant adverse consequences (Table 4).Three general principles apply to the therapy of metabolic alkalosis: correct true volume depletion, correct K+ depletion, and correct Cl− depletion (in Cl−-responsive metabolic alkalosis). For patients who have true volume depletion, fluid administration of normal saline replaces the Cl− and free water deficits. Potassium chloride administration for patients who have concurrent hypokalemia is an important component of treatment. This agent becomes particularly helpful in patients who are edematous due to heart failure or cirrhosis and cannot receive sodium chloride because an infusion can increase the degree of edema. Another method for treating metabolic alkalosis in an edematous patient is to administer acetazolamide, a carbonic anhydrase inhibitor, which causes a mild increase in production of urine that has high HCO3− content, thus reacidifying the blood. Correcting metabolic alkalosis (usually diuretic-induced) may be particularly important for intubated patients who have chronic respiratory acidosis. The higher pH caused by the metabolic alkalosis subsequently impairs the respiratory drive and leads to hypoventilation that exacerbates hypoxemia, delaying weaning and extubation. In these patients, metabolic alkalosis usually is corrected by enteral supplements of potassium chloride or sodium chloride. Very rarely, in the intensive care unit setting, the metabolic alkalosis can be so severe that it impairs weaning from mechanical ventilation. In these circumstances, intravenous infusion of hydrogen chloride can correct the alkalosis.Measuring the urinary Cl− is the preferred method for assessing the renal response to Cl− therapy. For patients experiencing Cl− depletion (urinary Cl− <10 mEq/L [10 mmol/L]) (eg, GI losses, diuretic therapy, and sweat losses in cystic fibrosis), every attempt should be made to correct hypochloremia. Conditions that cause metabolic alkalosis due to high aldosterone concentrations are unresponsive to Cl− and are associated with high urine Cl− concentrations.Minimizing continuing acid and chloride losses by excessive nasogastric fluid drainage with a histamine2 blocker or proton pump inhibitor also may be helpful.As noted, chemoreceptor analysis of arterial pH and Pco2 allows for centrally mediated adjustments in minute ventilation to maintain arterial Pco2 near 40 mm Hg. Primary respiratory disturbances in acid-base equilibrium may result from different pathologic scenarios. Arterial Pco2 rises abnormally (respiratory acidosis) if systemic CO2 production exceeds the ventilatory capacity or when efficient ventilation is inhibited by intrinsic or acquired conditions. Conversely, arterial Pco2 decreases abnormally (respiratory alkalosis) in response to physiologic disorders that result in excessive ventilation. Both respiratory acidosis and alkalosis may appear in association with other metabolic acid-base disturbances, often making accurate diagnosis and treatment of the underlying disease difficult to achieve. Respiratory acidosis occurs when arterial Pco2 increases and arterial pH decreases due to a reduction in alveolar minute ventilation or, less commonly, an excessive increase in CO2 production. Acute respiratory acidosis occurs with an acute elevation in Pco2 as a result of sudden limitation or failure of the respiratory system. Chronic respiratory acidosis is due to more indolent increases in Pco2 as a consequence of systemic disease over the course of several days. Reduction in minute ventilation can result from depression of central nervous system (CNS) respiratory drive, anatomic obstruction of the respiratory tract, or intrinsic or acquired impairments of normal thoracic excursion (Table 5).The body's compensatory changes in response to acute respiratory acidosis initially are limited to buffering via systemically available cellular HCO3− stores. Because of this limitation, serum HCO3− concentrations rise acutely by only 1 mEq/L (1 mmol/L) for every 10-mm Hg elevation in arterial Pco2. In response to chronic respiratory acidosis, the kidney retains HCO3− and secretes acid, an alteration in function that takes several (3 to 5) days to have a noticeable physiologic effect. Eventually, in chronic respiratory acidosis, serum HCO3− concentrations ultimately rise by approximately 3.5 mEq/L (3.5 mmol/L) for every 10-mm Hg elevation in arterial Pco2.Respiratory acidosis can affect both the CNS and cardiovascular system adversely. CNS effects include increased cerebral blood flow and increased intracranial pressure, which can present clinically as disorientation, acute confusion, headache, and mental obtundation. Cardiovascular effects include peripheral vasodilation and tachycardia. Severe hypoventilation leads to higher arterial Pco2 and more severe hypoxemia. Hypoxemia may be partially compensated by improved tissue extraction of oxygen via an acute acidosis-mediated rightward shift in the oxyhemoglobin dissociation curve and release of oxygen to the tissues. However, as respiratory acidosis persists, a reduction in red blood cell 2,3 diphosphoglycerate (an organophosphate created in erythrocytes during glycolysis) results in a shift of the curve to the left and an increase of hemoglobin affinity for oxygen.Treatment of respiratory acidosis usually focuses on correcting the primary disturbance. Immediate discontinuation of medications that suppress central respiratory drive or administration of appropriate reversal agents should be considered. Noninvasive ventilation or intubation with mechanical ventilation may be necessary to achieve adequate alveolar ventilation and appropriate reduction in arterial Pco2. As arterial Pco2 is corrected, individuals who experience excessive Cl− depletion may subsequently suffer poor renal clearance of HCO3−, leading to a concomitant state of metabolic alkalosis. Respiratory alkalosis occurs when there is reduction in arterial Pco2 and elevation in arterial pH due to excessive alveolar ventilation. Causes of excessive alveolar ventilation include medication toxicity, CNS disease, intrinsic lung diseases, and hypoxia (Table 6).Compensatory changes in response to respiratory alkalosis involve renal excretion of HCO3. As in respiratory acidosis, renal compensation improves as the disorder persists. Serum HCO3− concentrations decline by 2 mEq/L (2 mmol/L) for every 10-mm Hg decrease in arterial Pco2 in acute respiratory alkalosis. In chronic respiratory alkalosis, serum HCO3− concentrations decline by 4 mEq/L (4 mmol/L) for every 10-mm Hg decrease in arterial Pco2.Adverse systemic effects of respiratory alkalosis include CNS and cardiovascular disturbances. Respiratory alkalosis often provokes increased neuromuscular irritability, manifested as paresthesias or carpopedal spasms. In addition, cerebral blood vessels vasoconstrict acutely and impede adequate cerebral blood flow. Myocardial contractility may be diminished and cardiac arrhythmias may occur. The oxyhemoglobin dissociation curve shifts to the left in response to acute respiratory alkalosis, impairing peripheral oxygen delivery. Treatment of respiratory alkalosis centers on correcting the underlying systemic cause or disorder. Close assessment of oxygenation status and correction of hypoxemia via oxygen administration is paramount. Acute hyperventilation syndrome often is treated simply by having the patient breathe into a paper bag. To prevent high altitude-associated respiratory alkalosis, slow ascent to allow for acclimatization is recommended; administration of acetazolamide before ascent should be considered. The only cure for acute mountain sickness, once it has developed, is either acclimatization or descent. However, symptoms of acute mountain sickness can be reduced with acetazolamide and pain medications for headaches.

After completing this article, readers should be able to: Acute respiratory failure describes any impairment in oxygenation or ventilation in which the arterial oxygen tension falls below 60 mm Hg (acute hypoxemia), the carbon dioxide tension rises above 50 mm Hg (acute hypercarbia, hypercapnia) and the pH drops below 7.35, or both. For patients who have underlying chronic respiratory failure, acute hypercarbia can be diagnosed by an increase in Pco2 by 20 mm Hg from baseline. From a functional standpoint, respiratory failure is defined as the inability of the respiratory system to meet the metabolic needs of the tissues.The incidence of respiratory failure in pediatrics is inversely related to age. Two thirds of the cases of respiratory failure in children occur in the first postnatal year, and one half are seen in the neonatal period.The higher incidence of respiratory failure in infants has several developmental explanations. First, the airway is small and, with its narrowest point in the subglottic area, the infant's cone-shaped larynx is a likely site for obstruction. Second, the thoracic cage in infants is soft, with the ribs positioned horizontally, a mechanical disadvantage for chest expansion. Third, due to marginal energy stores in infants, the diaphragm fatigues easily. Fourth, the immature nervous system often triggers bradypnea/apnea. Finally, the infant's lower airways are small and compliant and easily prone to obstruction.A multitude of conditions can lead to respiratory failure (Table 1). Based on the location of the primary derangement, conditions can be classified as lung disorders, mechanical impairment of ventilation, airway-narrowing disorders, failure of the central nervous system to control respiration, and failure to meet the increased oxygen needs of the tissues. For teaching purposes, the various pathophysiologic mechanisms that lead to respiratory failure can be separated into failure of oxygenation (hypoxia) and failure of ventilation (hypercarbia).Pao2 is decreased in respiratory failure due to either an imbalance of ventilation and perfusion (V/Q matching) (most frequent) or impairment of oxygen diffusion at the level of the alveolar-capillary membrane (rare). To aid in understanding the concept of V/Q matching, ventilation and perfusion can be compared to two gears working together. If one gear spins more slowly than the other, malfunction occurs (Fig. 1). Using this model, if ventilation becomes zero relative to perfusion, intrapulmonary shunt occurs and deoxygenated blood mixes with the rest of the oxygenated blood.Oxygen delivery to tissues is a complex process that includes oxygenation at the level of the alveoli of hemoglobin and transport and delivery of the oxygen at the cellular level. Depending on the malfunctioning link that leads to low oxygen delivery, hypoxia can be classified as anoxic, anemic, stagnant, and cytochemical. Anoxic hypoxia occurs when the underlying disturbance exists at the gas exchange (respiratory) level. Anoxic hypoxia can be oxygen-sensitive, with clinical improvement occurring with increased inspired oxygen. When anoxic hypoxia is the result of a shunt (intrapulmonary or intracardiac), increasing the inspired oxygen does not lead to clinical improvement. Anemic hypoxia occurs when oxygen-carrying capacity is impaired, as with anemia (low hemoglobin) or insufficient functional hemoglobin (hemoglobinopathies). Oxygen delivery is further dependent on adequate blood flow. Stagnant hypoxia results when total blood flow is decreased (eg, heart failure) or maldistributed (eg, septic shock). At the capillary level, oxygen dissociates from oxyhemoglobin and diffuses into the surrounding area, where it is used by tissues. When this process malfunctions because of either exogenous or endogenous factors, cytochemical hypoxia occurs. An example of exogenous cytochemical hypoxia is toxin ingestion (eg, cyanide) that blocks oxygen use at the mitochondrial level.Appropriate ventilation is determined by minute ventilation, a product of respiratory rate and alveolar tidal volume. Ventilatory failure occurs in conditions that decrease tidal volume (shallow breathing) or respiratory rate (bradypnea), thereby decreasing carbon dioxide removal. In reality, failure to oxygenate and ventilate usually blends in respiratory failure.A 4-month-old, previously healthy baby is seen in December for fever, a 4-day history of nasal congestion, and progressive difficulty breathing. Vital signs are: heart rate of 169 beats/min, respiratory rate of 56 beats/min, blood pressure of 126/56 mm Hg, and oxygen saturation on room air of 92%. The infant is crying but can be consoled. Physical examination reveals intercostal and subcostal retractions, tachypnea, bilateral wheezing, and coarse breath sounds. Capillary refill is brisk and the extremities are warm. A chest radiograph shows peribronchial cuffing and slight hyperinflation suggestive of viral pneumonitis. A swab for respiratory syncytial virus (RSV) is reported as positive. Supplemental oxygen is initiated, viral bronchiolitis is diagnosed, and the infant is admitted for monitoring. A few hours later, he becomes very agitated, flushed, and inconsolable. His heart rate is 189 beats/min, respiratory rate is 86 beats/min, and oxygen saturation is 92% on 3 L of oxygen administered by nasal canula. His work of breathing is significantly increased, as demonstrated by nasal flaring, grunting, head bobbing, and significant retractions. The infant is transferred to the intensive care unit for intubation and mechanical ventilation. Arterial blood gas before intubation shows a pH of 7.16 and Pco2 of 70 mm Hg. He is intubated and mechanically ventilated for 4 days.In this case, lower airway obstruction led to poor ventilation and respiratory failure. This case also illustrates the clinical manifestations of acute hypercapnia: flushing, agitation, and tachycardia (Table 2).It is important to note that RSV might cause respiratory failure by two different mechanisms: lower airway involvement (bronchiolitis), as in this case, and RSV-caused central apnea. The latter mechanism is seen more frequently in young infants than in older children.A 9-year-old child who has a history of Down syndrome, mitochondrial myopathy, and tracheostomy is admitted because of a 3-week history of decreased activity and increased somnolence. His respiratory rate is 35 beats/min with very shallow effort. Arterial blood gas reveals: pH, 7.33; Pco2, 62 mm Hg; Po2, 54 mm Hg; and HCO3, 28 mEq/L on room air (0.21 Fio2). Complete blood count reveals polycythemia with a hemoglobin of 15 g/dL (150 g/L) and hematocrit of 48% (0.48). The patient receives 100% oxygen, and subsequent arterial blood gas determination documents pH, 7.23; Pco2, 80 mm Hg; Po2, 118 mm Hg; and HCO3, 32 mEq/L. Chest radiograph reveals mild cardiomegaly and increased pulmonary markings suggestive of chronic lung disease (Fig. 2). Echocardiography shows mild pulmonary hypertension and right ventricular hypertrophy. The patient is placed on home mechanical ventilation to treat chronic respiratory failure.Increased work of breathing is the usual primary manifestation of respiratory failure. Patients who have under- lying myopathy lack the ability to mount this important compensatory mechanism for impending respiratory failure, and their physical findings may be misleading. As for this patient, such individuals present with tachypnea and very shallow breathing without retractions. The first blood gas result for this child is typical of chronic respiratory failure: chronic carbon dioxide retention (increased Pco2) leading to metabolic compensation (increased serum bicarbonate concentration, increased base excess), with the pH reflecting only mild acidosis. The second blood gas pattern exemplifies how administering 100% oxygen to patients who have chronic respiratory failure may lead to higher carbon dioxide retention. For patients who have chronic respiratory failure, the respiratory center is stimulated primarily by hypoxia. By improving oxygenation, the hypoxic drive of the respiratory center is blunted, and alveolar ventilation decreases, leading to a higher carbon dioxide concentration (acute respiratory failure on top of the existing chronic respiratory failure). Other important findings in this patient include polycythemia, pulmonary hypertension, and cor pulmonale, which represent possible but rare complications of chronic hypoxemia.The initial assessment of the patient in respiratory failure should focus on determining the urgency of medical intervention. Several clinical clues help discern who requires intubation and mechanical ventilation. In the hands of an experienced physician, this decision usually is reached within the first few minutes of the clinical encounter. The most helpful indicators are vital signs, work of breathing, and level of consciousness. The patient who exhibits very rapid respirations, significant retractions, head bobbing, nasal flaring, and grunting requires aggressive and urgent respiratory support. As the patient becomes increasingly fatigued, he or she has more shallow respirations, leading to lack of responsiveness and hypoxemia despite a high Fio2. Such ominous signs of respiratory failure or impending cardiorespiratory arrest should prompt emergent airway control and ventilatory support. Patients presenting with severe hemodynamic compromise, mottled extremities, and very low blood pressure that have caused a markedly decreased response to painful stimuli (impending cardiac arrest) also require emergent airway control, breathing, and circulatory support. Central nervous system disorders leading to decreased responsiveness also mandate emergent airway control and breathing support.If emergent intervention is not necessary, a more comprehensive history can be obtained and should focus on determining probable causes of the respiratory failure: previous fever and illness contacts, possible foreign body aspiration, and previous chronic lung disease (cystic fibrosis, asthma, prematurity). Causes of central hypoventilation (drug ingestion, head trauma, and seizures) also should be queried.Vital signs are extremely helpful in determining the severity of respiratory failure. In the otherwise healthy child, tachypnea is one of the earliest compensatory mechanisms for inadequate ventilation. The patient who presents with severe tachypnea and increased work of breathing (intercostal and substernal retractions) warrants immediate intervention and close monitoring. Bradypnea usually is an ominous sign reflecting failure of compensatory mechanisms and requires emergent intervention. Patients who have underlying neuromuscular disease may be unable to mount the usual signs of respiratory distress because they often lack the ability to increase the respiratory rate or produce retractions; rather, they present with shallow and ineffective respirations.Continuous monitoring of pulse oximetry has become an important tool for respiratory assessment and monitoring. Pulse oximetry is a noninvasive method widely used to assess oxygen saturation. It employs light absorption characteristic of oxyhemoglobin to estimate oxygen saturation of hemoglobin. A pulse oximetry saturation of 90% is associated with a Pao2 of 60 mm Hg, based on the sigmoid shape of the oxyhemoglobin dissociation curve.Pulse oximetry has several limitations. Because it measures saturation and not oxygen content or oxygen delivery, moderately low oxygen saturations in a patient who has anemia may be clinically significant. Anemia may lead to tissue hypoxia, despite a normal Pao2, as exemplified by the following equations: Sao2 can increase artificially when carboxyhemoglobin concentrations are high (eg, smoke inhalation), decrease artificially in the presence of intravenous dyes such as methylene blue, or increase or decrease artificially in the presence of high methemoglobin concentrations. Pulse oximetry is unreliable for patients who have decreased tissue perfusion (shock, hypovolemia, or hypothermia) due to poor signal detection. The pulse rate registered on the oximeter should match the patient's heart rate. Monitoring oxygen saturation alone in patients who have respiratory failure might be misleading because a patient receiving supplemental oxygen can maintain good oxygenation despite retaining carbon dioxide. Cyanosis rarely is a helpful sign in the assessment of respiratory failure because it occurs late in the course of respiratory failure. Patients who have anemia develop cyanosis only at much lower levels of Pao2 because cyanosis is related to the absolute amount of reduced hemoglobin. Also, conditions associated with poor perfusion, such as septic shock or cardiac failure, may mimic cyanosis.Heart rate usually parallels the work of breathing. Tachycardia typically is a compensatory mechanism for maintaining adequate oxygen delivery in the face of hypoxemia. Bradycardia develops because of severe hypoxemia and is a sign of impending cardiorespiratory arrest.Blood pressure usually is high when a patient is anxious. Low blood pressure is an ominous sign, suggesting decompensated shock, and should trigger the initiation of aggressive hemodynamic and respiratory support.Physical examination of the respiratory system starts with assessment of the work of breathing. Close monitoring and frequent reassessments in an intensive monitoring setting are paramount. Again, patients who have neuromuscular disease present with shallow, ineffective respirations. Decreased work of breathing with more superficial respirations along with worsening mental status are ominous signs and signal severe respiratory failure and impending arrest.Clinical findings suggestive of increased work of breathing include nasal flaring, intercostal and substernal retractions (Fig. 3), head bobbing (Fig. 4), respiratory pauses, grunting, and thoracoabdominal asynchrony (Fig. 5).During inspection of the chest wall, the shape of the thoracic cage and spine should be noted. Asymmetric chest movements or tracheal deviation raise the question of a unilateral pathologic process such as severe pleural effusion or pneumothorax.Auscultation of the chest assesses the adequacy of air exchange, symmetry of breath sounds, and presence of abnormal breath sounds such as wheezing or crackles. Very decreased breath sounds signal severe reduction in air exchange. Stridor usually is an inspiratory sound that suggests narrowing of the upper airway in conditions such as croup or laryngomalacia. Wheezing typically is an expiratory sound, associated with prolonged expiration, and indicative of lower airway disorders such as asthma, bronchiolitis, or bronchomalacia. Asymmetric wheezing should raise the suspicion of a foreign body aspiration or a mass obstructing the airway. Crackles indicate an alveolar process such as pneumonia.Examination of the heart for abnormal heart sounds may offer clues to possible congenital or acquired heart disease. Measurement of blood pressure in all four extremities along with palpation of brachial and femoral pulses helps to rule out aortic coarctation.Assessment of muscle strength and gait is important for diagnosing several illnesses that may lead to chronic respiratory failure. Muscle strength is decreased in myopathies such as Duchene muscular dystrophy and some mitochondrial diseases. In infancy, delayed motor milestones often provide the first clues to a severe myopathy. Lack of attaining head control at an appropriate age may suggest spinal muscular atrophy. Loss of motor milestones also raises the suspicion of a myopathy. Acute ascending paralysis may suggest Guillain-Barré syndrome, and acute generalized muscle weakness may suggest botulism as causes of respiratory failure.Changes in mental status, either agitation or somnolence, can be signs of respiratory failure. Agitation may be due to hypoxemia, and somnolence may be due to hypercarbia (Table 2). Assessment using the Glasgow Coma Scale (GCS) is important. A decreased GCS score indicates impaired neurologic function, which may be caused by any of three mechanisms: direct neurologic insult (meningitis, traumatic brain injury), hypoxemia and hypercarbia due to respiratory failure or poor perfusion, and poor oxygen delivery in shock. Altered mental status leads to an inability to control the airway and secretions (depressed respiratory drive, depressed gag reflex). A GCS score below 8 is an indication for airway control by intubation and mechanical ventilation.Both laboratory and radiographic investigations are important tools for assessing and monitoring the response to the management of respiratory failure. However, the necessity for immediate intervention should not be delayed pending the results of the blood gas or chest radiograph.The arterial blood gas accurately assesses the extent of hypoxemia or hypercarbia (Table 3). The results of blood gas analysis should be correlated with the clinical picture (Table 4). A normal Pco2 in a patient demonstrating very high work of breathing and severe tachypnea is not reassuring; this finding reflects respiratory failure (patient is maintaining normal Pco2 by breathing hard and fast, and exhaustion is bound to occur) and demands appropriate intervention. Similarly, normal Pco2 in a patient who has severe metabolic acidosis and tachypnea is a sign of impending respiratory failure.The complete blood count may offer clues to the cause of respiratory failure. Anemia can be associated with chronic illness and polycythemia with obstructive sleep apnea.A chest radiograph is an important tool used to confirm a diagnosis suspected on clinical grounds, such as pneumonia, pulmonary edema, pneumothorax, or pleural effusion.Pulmonary function testing (PFT) has been a major step forward in the assessment of the functional status of the respiratory system because it accurately measures the volume of air that can be moved and how rapidly the air can flow. PFT provides objective measurements that can be used to characterize the respiratory disease, assess its severity, and document the course of the illness and response to therapy.Unrecognized respiratory failure is the leading cause of cardiopulmonary arrest in children. Therefore, early diagnosis and close monitoring are paramount. Required interventions range from close monitoring and supplemental oxygen to full mechanical ventilatory support. If the rapid initial assessment warrants emergent intervention, preparation for intubation and mechanical ventilation should be undertaken.Bag-mask ventilation with 100% oxygen is an important initial step to ensure proper ventilation and preoxygenation before the intubation. This step also allows time to gather all the necessary equipment (appropriate size endotracheal tube, large-bore suction, laryngoscope, carbon dioxide detector, and intubation drugs). The key to successful intubation is calm and controlled performance. Depending on the clinical setting, intubation is performed best by medical personnel who have the highest available expertise in performing the procedure (critical care physicians, anesthesiologists, emergency medical services personnel). The patient should be well sedated. Neuromuscular blockade is useful, except in rare situations when a very difficult airway is anticipated (eg, Pierre Robin syndrome, anterior mediastinal mass). In cases of a difficult airway, the use of a laryngeal mask airway (LMA) should be considered very early. Multiple unsuccessful intubation attempts should be avoided.The LMA is an alternative airway device that can be used for emergent airway support. It consists of an inflatable silicone mask and rubber connecting tube. The device is inserted blindly into the pharynx, forming a low-pressure seal around the laryngeal inlet and permitting gentle positive-pressure ventilation. Use of the LMA allows rapid access and does not require laryngoscopy or muscle relaxants, making it a reasonable option for temporary control of the very difficult airway. However, the LMA does not fully protect against aspiration in the patient who has not been fasting.If emergent intervention it is not warranted, a wide array of support can be offered. For mild cases, the only required intervention may be supplemental oxygen delivered via nasal canula. When oxygen requirements are high, oxygen can be delivered by a nonrebreather mask (delivers high-flow oxygen at 10 to 15 L/min). Rarely, pediatric patients who have chronic respiratory failure depend on hypoxemia for the respiratory drive, and providing more oxygen may decrease the drive to breathe.Noninvasive mechanical ventilation can be used in selected patients in the intensive care unit. Patients who could benefit from this intervention usually have good respiratory drive and increased work of breathing. However, such patients must be monitored closely because noninvasive mechanical ventilation is not designed for those who are developing apnea or whose mental status is altered.Continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) are modes of noninvasive mechanical support. The positive pressure is delivered through a tight-fitting facemask. CPAP provides only a single level of airway pressure maintained throughout the respiratory cycle, thereby helping to prevent alveolar collapse. BiPAP provides an inspiratory positive airway pressure for ventilator assistance and expiratory positive airway pressure to facilitate and maintain lung expansion. The risk of developing pressure sores on the face limits prolonged use of noninvasive mechanical ventilation for 24 hours per day. BiPAP at night can be used at home for patients who have chronic respiratory failure to postpone the need for tracheostomy or home mechanical ventilation or who choose not to use other interventions.Conventional treatment of acute respiratory failure involves positive-pressure ventilation with supplemental oxygen. Newer generations of mechanical ventilators offer multiple modes and features. Because no clear data exist on the appropriate ventilator mode for a particular condition, managing mechanical ventilation remains part of the art of practicing medicine. Several accepted general concepts of mechanical ventilation contribute to outcome.First are considerations of the mode of ventilation and the inspiratory flow pattern. In assist control (AC) mode, each breath given is a full tidal volume initiated when the patient takes a small triggering breath. Because AC gives a full breath each time, it is not appropriate for weaning a patient from mechanical ventilation.At the other end of the spectrum is synchronized intermittent mechanical ventilation with pressure support (SIMV-PS), which delivers a combination of full support breaths and patient-initiated spontaneous breaths that have partial support, so some work is done by the ventilator and some by the patient. The controlled breaths can be limited either by reaching a preset pressure limit (pressure control) or a preset volume limit (volume control).It is important to facilitate optimal patient-ventilator interaction while keeping the adverse effects of deep sedation to a minimum. In addition, ventilation with elevated oxygen concentrations and airway pressure has been shown to worsen lung injury, known as ventilator-induced lung injury (VILI). Thus, the goal is to minimize lung injury while providing effective ventilation and oxygenation. An Fio2 greater than 0.6 used for longer than 6 hours is believed to add oxidative stress to the ventilated lung and contribute to VILI.In 2000, the Acute Respiratory Distress Syndrome (ARDS) network reported improved outcome in adults treated with low tidal volume ventilation (6 mL/kg) compared with those treated with high tidal volume (12 mL/kg). It is unclear whether 6 mL/kg is superior to 8 mL/kg and whether results of these studies can be extrapolated to pediatric patients. At present, use of the lowest possible pressures and volumes to maintain acceptable ventilation and oxygenation is recommended. Because maintaining appropriate oxygen delivery to the major organs is most important, the volumes and pressures used for mechanical ventilation must be high for some very ill patients.The instillation of surfactant or inhaled nitric oxide (iNO) can supplement mechanical ventilation in carefully selected patients. Intratracheal instillation of surfactant in preterm infants has significantly improved the outcome of respiratory distress syndrome of prematurity and, therefore, has become the standard of care. The use of surfactant for the treatment of ARDS in the pediatric age group still is controversial and currently the subject of a multicenter trial. iNO is an adjunctive therapy administered to patients who have documented or suspected pulmonary hypertension and significant oxygenation failure.If adequate gas exchange cannot be achieved with conventional mechanical ventilation, high-frequency ventilation (HFV) is a good therapeutic option. With growing use, HFV no longer represents a nonconventional mode of ventilation. The basic principle of HFV is the delivery of tidal volumes smaller than the dead space with a rate greater than 150 breaths/min. In a way, this “extreme” model of low tidal volume ventilation mitigates the deleterious effect of barotrauma and volutrauma associated with high tidal volume ventilation and high pressure changes. There is little agreement on selection criteria for patients who would benefit from HFV. In general, HFV should be considered in those who require maximum Fio2 and high airway pressure (peak pressures higher than 35 mm Hg) to meet adequate oxygenation for longer than a few hours.When all options have failed to provide adequate gas exchange and hemodynamic support, strong consideration should be given to extracorporeal membrane oxygenation (ECMO). The general indication for ECMO in patients who have respiratory failure is a reversible underlying illness that has failed conventional ventilator strategies. ECMO is a modified heart-lung machine that provides total gas exchange through an extracorporeal system, allowing the lungs to “rest” and not be subjected to the additional lung injury caused by high-pressure ventilation. Survival after ECMO is determined primarily by the underlying illness. For example, in neonates, meconium aspiration syndrome requiring ECMO carries the best prognosis, with a survival rate of 94%, but pediatric patients undergoing ECMO for viral pneumonia have an average survival rate of approximately 64%. Selecting the patients for whom ECMO is indicated has been controversial, particularly because of ongoing improvements in conventional strategies.Weaning from mechanical ventilation is achieved gradually as the underlying pathologic process resolves. Determining extubation readiness should involve assessment not only of the patient's pulmonary status but also the overall clinical status. Neurologic considerations are important, including assessment of the patient's sedation status, ability to protect the airway, and capability of maintaining an appropriate respiratory drive. Cardiovascular considerations include the degree of hemodynamic support and anticipated effect of increased work of breathing on cardiac function. Airway edema and airway abnormalities are important factors that can lead to extubation failure.

RATIONALE:Advances in spirometry measurement techniques have made it possible to obtain measurements in children as young as 3 years of age; however, in practice, application remains limited by the lack of appropriate reference data for young children, which are often based on limited population-specific samples. OBJECTIVES:We aimed to build on previous models by collating existing reference data in young children (aged 3-7 yr), to produce updated prediction equations that span the preschool years and that are also linked to established reference equations for older children and adults. METHODS:The Asthma UK Collaborative Initiative was established to collate lung function data from healthy young children aged 3 to 7 years. Collaborators included researchers with access to pulmonary function test data in healthy preschool children. Spirometry centiles were created using the LMS (lambda, micro, sigma) method and extend previously published equations down to 3 years of age. MEASUREMENTS AND MAIN RESULTS:The Asthma UK centile charts for spirometry are based on the largest sample of healthy young Caucasian children aged 3-7 years (n = 3,777) from 15 centers across 11 countries and provide a continuous reference with a smooth transition into adolescence and adulthood. These equations improve existing pediatric equations by considering the between-subject variability to define a more appropriate age-dependent lower limit of normal. The collated data set reflects a variety of equipment, measurement protocols, and population characteristics and may be generalizable across different populations. CONCLUSIONS:We present prediction equations for spirometry for preschool children and provide a foundation that will facilitate continued updating.

based on either 1 major risk factor (atopic dermatitis or ≥1 parent with asthma) or 2 of 3 minor risk factors (allergic rhinitis, eosinophilia [≥4%], or wheezing without a cold). This original API was based on data from the Tucson Children’s Respiratory Study, which suggested that children who experience frequent wheezing at an early age have an increased risk of having asthma between the ages of 6 and 13 years if the API criteria are met. A modified API defines a positive test as 4 or more exacerbations of wheezing in the past 12 months with at least 1 physician-confirmed exacerbation, adds allergic sensitization to at least 1 aeroallergen among the major criteria, and replaces allergic rhinitis as a minor criterion with allergic sensitization to milk, eggs, or peanuts. In early childhood, asthma is often underdiagnosed because the symptoms can vary widely and are similar to those of other common childhood illnesses, including bronchitis, viral lower respiratory infection, and recurrent upper respiratory tract infections. In many cases, the lack of a correct diagnosis of asthma results from the lack of understanding of the nonwheezing manifestations of asthma, failure to recognize symptom patterns/chronicity, attributing symptoms to a series of acute illnesses (eg, recurrent bronchiolitis, pneumonia, bronchitis), and a reluctance to label the patient as asthmatic. Clinical signs and symptoms of episodic or chronic wheezing, coughing, or breathlessness that may indicate a diagnosis other than asthma are presented in Table 1. The clinical diagnosis of asthma is based on the findings of a characteristic symptom complex for childhood asthma; this is a template for the disease. Symptoms consistent with asthma in young children include recurrent wheeze associated with triggers, such as viral infection or exercise, cough, signs of a secretion defect (ie, excess secretion, poor clearance, chronic bronchitis, or recurrent pneumonia), and increased bronchial hyperreactivity, such as cough or wheeze with mild exercise, as assessed by pulmonary function tests Asthma is a heterogenous inflammatory disease characterized by recurrent episodes of symptoms such as wheezing, breathlessness, chest tightness, and cough that commonly begin in early life. Initial asthma symptoms are typically episodic and occur in association with viral respiratory tract infections. Early episodic wheezing can result in 2 disease patterns: remission of symptoms during the preschool years and progression to persistent asthma. Establishing a diagnosis of asthma in young wheezing patients can be challenging because the type, severity, and frequency of asthma signs and symptoms vary widely among, and sometimes within, individual children. Knowing when and how to treat episodic wheeze, assessing the risk of asthma progression in wheezing patients, choosing the most effective controller regimen in patients once asthma is diagnosed, and deciding when to terminate controller therapy also can be difficult decisions for physicians. This review provides literature-based and clinical experience-based recommendations for the management of wheeze and diagnosis and management of asthma in young children.

Considering that it is such a common disease, the diagnosis and severity classification of asthma is extraordinarily difficult. Gross put it well: “It’s like love, we all know what it is, but who would trust anybody else’s definition?”1Gross N.J. What is this thing called love?, or defining asthma.Am Rev Respir Dis. 1980; 121: 203-204PubMed Google Scholar The National Asthma Education and Prevention Program (NAEPP) guidelines suggest the diagnosis of asthma should be in large part based upon the medical history and physical examination.2National Asthma Education and Prevention ProgramExpert Panel Report II: Guidelines for the Diagnosis and Management of Asthma Publication 97-4051. National Institutes of Health, Bethesda, MD1997Google Scholar However, these guidelines rightly go on to point out that “patients with asthma are heterogeneous and present signs and symptoms that vary widely from patient to patient as well as within each patient over time.” Subtle variations in the interpretation of an individual patient’s signs and symptoms may greatly influence not only whether the diagnosis of asthma is made, but also affect the aggressiveness of the ensuing treatment. Thus, we can think of asthma as a complex mosaic, with the history and exam as only two tiles in a much larger diagnostic picture.See related article, p 457 See related article, p 457 In order to provide more objective diagnostic criteria, the NAEPP guidelines advise routine use of spirometry to aid in the diagnosis of asthma. Indeed, the three facets of history, exam and low baseline forced expiratory volume in 1 second (FEV1) remain the standard for diagnosing asthma in adults. However, in children there are convincing data showing that baseline FEV1 is not a good measure of the presence of asthma or its severity. In the Childhood Asthma Management Program study, which evaluated 1041 children with mild to moderate asthma, more than 50% of the patients had moderate persistent asthma as defined by frequency of symptoms.3Spahn J.D. Cherniack R. Paull K. Gelfand E.W. Is forced expiratory volume in one second the best measure of severity in childhood asthma?.Am J Respir Crit Care Med. 2004; 169: 784-786Crossref PubMed Google Scholar Asthma was well documented in these patients over the 5-year life of the study, yet the prebronchodilator FEV1 at the start of the study was clearly normal at 94% of predicted. A much quoted paper by Fuhlbrigge et al4Fuhlbrigge A.L. Weiss S.T. Kuntz K.M. Paltiel A.D. Forced expiratory volume in 1 second percentage improves the classification of severity among children with asthma.Pediatrics. 2006; 118: e347-e355Crossref PubMed Scopus (74) Google Scholar found those children with FEV1 values of <60% predicted had a 70% likelihood of having an asthma exacerbation in the following year. In those with FEV1 values >80%, the likelihood of experiencing an exacerbation was reduced to 25% to 30%. These data have been interpreted as showing that attacks can be predicted based on percent predicted FEV1. Yet it is perhaps more important to note that 94% of the FEV1 values in this population of asthmatic children were normal, meaning that 80% of asthma attacks occurred in children with a normal baseline FEV1. The limits of using FEV1 alone in the assessment of childhood asthma were also demonstrated by Bacharier et al,5Bacharier L.B. Strunk R.C. Mauger D. White D. Lemanske Jr, R.F. Sorkness C.A. Classifying asthma severity in children: mismatch between symptoms, medication use, and lung function.Am J Respir Crit Care Med. 2004; 170: 426-432Crossref PubMed Scopus (329) Google Scholar who found a lack of association among asthma symptom severity, intensity of medication therapy, and percent predicted FEV1 in asthmatic children. Bronchial lability may be a more useful measure in the diagnosis of childhood asthma. Proving the existence of airway hyperreactivity in the context of clinical symptoms begins to add more details to our asthma mosaic. This is not a new concept. Exaggerated bronchodilation followed by bronchoconstriction in response to exercise—the so-called “bronchial lability index”—was described in asthmatic children by Jones.6Jones R.S. Assessment of respiratory function in the asthmatic child.Br Med J. 1966; 2: 972-975Crossref PubMed Scopus (56) Google Scholar This and other early studies observed that pediatric asthmatic airways are remarkably labile in both directions when appropriately stimulated. The study by Gallant et al7Galant S.P. Morphew T. Amaro S. Liao O. The value of the bronchodilator response in assessing controller-naïve asthmatic children.J Pediatr. 2007; 151: 457-462Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar published in this issue of The Journal shows that detecting broncholability by measuring the response to an inhaled bronchodilator can aid in the diagnosis of asthma in children. The authors demonstrate that using 9% as a distinct cutoff value for improvement in FEV1 after inhaled albuterol (either 180 μg by metered dose inhaler or 2.5 mg by nebulizer) can distinguish a group of known asthmatic children from those who are normal by history. The findings of Gallant et al support the earlier study by Dundas et al8Dundas I. Chan E.Y. Bridge P.D. McKenzie S.A. Diagnostic accuracy of bronchodilator responsiveness in wheezy children.Thorax. 2005; 60: 13-16Crossref PubMed Scopus (62) Google Scholar that determined that a 9% cutoff for the bronchodilator response (BDR) to 400 μg of salbutamol (albuterol) provided the greatest balance between sensitivity and specificity in separating wheezers from nonwheezers in a group of London schoolchildren (race not described). However as stated by Dundas et al, the diagnostic value of a 9% BDR cutoff will vary with the prevalence of wheezing in the study population. Gallant et al studied a group of clinically diagnosed asthmatic children with a presumed incidence of wheezing of 100%. This exaggerated the difference between this study group and the comparator group to some degree. As a diagnostic test, BDR will be used in populations in which the incidence of wheezing may be much lower and the distinction between asthmatics and nonasthmatics is less clear. Without a prospective assessment of the 9% BDR cutoff value in an unselected cohort of subjects, the findings of Gallant et al still leave us several steps away from implementing BDR as a diagnostic test for asthma. Although the ethnic composition of Gallant et al’s population is described as primarily Hispanic, the racial composition is not fully described. As recognized by the authors, extrapolating the 9% BDR cutoff to similarly aged African-American, Caucasian, or mixed populations is difficult, especially in light of the fact that different genetic groups respond to bronchodilator medications differently.9Tsai H.J. Shaikh N. Kho J.Y. Battle N. Naqvi M. Navarro D. et al.Beta 2-adrenergic receptor polymorphisms: pharmacogenetic response to bronchodilator among African-American asthmatics.Hum Genet. 2006; 119: 547-557Crossref PubMed Scopus (77) Google Scholar The diagnostic BDR cutoff point certainly may be lower in children with less sensitivity to beta-agonist medications than the general population. The effect of baseline lung function on BDR measurement also must be considered, as Gallant et al acknowledge. This relationship was described by Sly,10Sly R.M. Exercise-related changes in airway obstruction: frequency and clinical correlates in asthmatic children.Ann Allergy. 1970; 28: 1-16PubMed Google Scholar who noted that the greatest percent increase in peak expiratory flow rate (PEFR) with treadmill exercise was seen in those asthmatic children with the lowest baseline PEFR. Where a child stands in relation to his or her maximum lung function on the day of testing will contribute to his or her ability to respond. A child already at his or her personal maximum for FEV1 would not exhibit a response to a bronchodilator even if he or she were asthmatic. In a disease as variable as asthma, this may prove a difficult hurdle to cross to use BDR as a diagnostic criterion. The present study used 2 distinct methods of delivering the albuterol medication—some subjects used a metered dose inhaler, whereas others received the medication via wet nebulization. Although the quantitative difference in medication delivery between these 2 methods of medication administration may be small, the effect on BDR is not known. Using a single delivery method may have resulted in different outcomes. The dose and mode of delivery of beta-agonists are likely to play some role in the degree of observed bronchodilation and will need to be standardized to make this a clinically helpful test. Gallant et al have presented a very sound idea for helping pediatric clinicians diagnose asthma. They have shown that BDR distinguishes between asthmatics and nonasthmatics better than baseline FEV1 alone, and that a combination of a high BDR and a low FEV1 is best for discriminating asthmatics from nonasthmatics (although these characteristics may be linked). Finally, and perhaps most importantly, they have demonstrated another way in which lung function testing can be helpful in the difficult process of diagnosing and managing asthma in children. Spirometric evaluation is relatively simple to perform in many preschool-age and nearly all school-age children.11Eigen H. Bieler H. Grant D. Christoph K. Terrill D. Heilman D.K. et al.Spirometric pulmonary function in healthy preschool children.Am J Respir Crit Care Med. 2001; 163: 619-623Crossref PubMed Scopus (221) Google Scholar We believe that with further study, BDR testing will prove to be an important tool in our efforts to complete the asthma mosaic. Value of the Bronchodilator Response in Assessing Controller Naïve Asthmatic ChildrenThe Journal of PediatricsVol. 151Issue 5PreviewTo define the bronchodilator response (BDR) cutoff point that best identified asthma to determine the frequency of abnormal spirometry results across severity. Full-Text PDF

Nicole Beydon, Stephanie D. Davis, Enrico Lombardi, Julian L. Allen, Hubertus G. M. Arets, Paul Aurora, Hans Bisgaard, G. Michael Davis, Francine M. Ducharme, Howard Eigen, Monika Gappa, Claude Gaultier, Per M. Gustafsson, Graham L. Hall, Zoltán Hantos, Michael J. R. Healy, Marcus H. Jones, Bent Klug, Karin C. Lødrup Carlsen, Sheila A. McKenzie, François Marchal, Oscar H. Mayer, Peter J. F. M. Merkus, Mohy G. Morris, Ellie Oostveen, J. Jane Pillow, Paul C. Seddon, Michael Silverman, Peter D. Sly, Janet Stocks, Robert S. Tepper, Daphna Vilozni, and Nicola M. Wilson, on behalf of the American Thoracic Society/ European Respiratory Society Working Group on Infant and Young Children Pulmonary Function Testing

Early inhaled corticosteroid treatment improves symptom control and pulmonary function in children with asthma; however, long-term safety data are limited in infants and young children. This study assessed the long-term safety of budesonide inhalation suspension (BIS) in young children with persistent asthma. To continue to provide BIS to children who needed it—prior to US Food and Drug Administration approval—children 8 years of age or younger with mild, moderate, or severe persistent asthma who previously completed a 52-week open-label study of BIS were enrolled in an additional multicenter, open-label study that was to be concluded upon BIS approval. Patients already receiving BIS continued their current regimens. Patients younger than 4 years and those 4 years of age or older not receiving BIS at baseline started with total daily doses of 0.5 and 1.0 mg, respectively. BIS doses were adjusted throughout the study based on individual response. Adverse events and changes in laboratory parameters, vital signs, and physical examination findings were assessed. Of 198 enrolled patients, 152 (76.8%), 68 (34.3%), and 31 (15.7%) completed 1, 2, and 3 years of BIS treatment (mean daily dose 0.62±0.32 mg), respectively. One hundred sixty-six (83.8%) patients experienced an adverse event, of which 8.6% were considered by the investigator to be drug related. Adverse events were those typically occurring in a pediatric asthma population, with respiratory infection (49.0%) and sinusitis (25.3%) occurring at the greatest incidence. Only 2 patients withdrew due to adverse events. Mean changes in laboratory test results and physical examination findings were not clinically important throughout the study. Long-term BIS treatment is well tolerated in young children with persistent asthma, with a safety profile similar to that of short-term administration.

BACKGROUND:Cystic fibrosis causes exocrine pancreatic insufficiency, leading to malabsorption. Supplemental pancreatic enzyme therapy alleviates the concomitant malnutrition experienced by cystic fibrosis patients. It is recognized that patients experience variations in clinical response to different brands of enzymes. This has prompted the US Food and Drug Administration to require that enzyme supplements be subjected to New Drug Applications.AIM:To investigate the safety and efficacy of supplemental pancreatic enzyme therapy in cystic fibrosis subjects.METHODS:We compared two doses of one formulation of enteric-coated pancreatic enzymes: Ultrase MT12 (12,000 lipase units per capsule) and Ultrase MT20 (20,000 lipase units per capsule), to placebo in two separate safety and efficacy studies.RESULTS:Mean total fat, protein and carbohydrate intake did not differ significantly between the groups. A significant difference in both fat and protein absorption occurred with the enzyme therapy groups. The Ultrase MT12 and Ultrase MT20 groups experienced a mean fat and protein absorption 79.4% and 83.8%, and 87.3% and 88.6%, respectively. No adverse events related to study drug were reported.CONCLUSIONS:This study further supports the use of enzymes to treat pancreatic insufficiency in cystic fibrosis. Excellent fat and protein absorption was achieved with minimal adverse events and safe doses.

Background: Patients with mild intermittent or mild persistent asthma represent 70% of asthma sufferers. Inhaled corticosteroids (ICSs) are the mainstay of treatment for persistent asthma, although many of the early clinical studies of these drugs included only patients with moderate to severe asthma.Objective: This article reviews the literature on the efficacy of budesonide in the treatment of mild persistent asthma, including newly diagnosed ICS-naive patients.Methods: Published data were identified by a MEDLINE search of the English-language literature from 1992 to 2002 using the terms budesonide plus efficacy or safety, both with and without the terms fluticasone or beclomethasone. An AstraZeneca reference database was also used to identify publications from the same period. Controlled, randomized studies that included patients with mild persistent asthma and early-treatment intervention were selected for inclusion.Results: Inhaled budesonide has been used for almost 20 years in the treatment and control of moderate to severe asthma. Studies involving patients with mild persistent asthma have demonstrated significant improvements in peak expiratory flow (PEF) rates (P < 0.01) and forced expiratory volume in 1 second (P < 0.016) values for adult, adolescent, and pediatric patients treated with budesonide compared with placebo. Budesonide therapy is effective when given once or twice daily via dry powder inhaler or nebulizer, even at a low starting dose (200 mug/d). No significant adverse events have been reported with budesonide within the dose range used to treat mild persistent asthma (200 to 400 mug/d). Significant improvements in PEF rates (P < 0.01) and significant reductions in the risk of exacerbations and the number of days with poorly controlled asthma have been reported for ICS-naive patients treated with budesonide compared with placebo (both P < 0.001). In the primary care setting, mild persistent asthma may be undertreated. Patients with mild persistent asthma benefit significantly from early treatment with budesonide (P < 0.05).Conclusions: Budesonide is effective and well tolerated in the treatment of mild persistent asthma in adults and children, including many patients whose primary care physicians do not think they require daily ICS treatment.