Objective To compare growth, feeding tolerance, and clinical and biochemical evaluations in human milk-fed preterm infants randomized to receive either an acidified or a nonacidified liquid human milk fortifier. Study design This prospective, controlled, parallel, multicenter growth and tolerance study included 164 preterm infants (<= 32 weeks of gestation, birth weight 700-1500 g) who were randomized to acidified or nonacidified liquid human milk fortifier from study day 1. the first day of fortification, through study day 29 or until hospital discharge. Results There was no difference in the primary outcome of weight gain from study days 1 to 29 (acidified liquid human milk fortifier, 16.4 +/- 0.4 g/kg/day; nonacidified liquid human milk fortifier. 16.9 +/- 0.4 g/kg/day). However, in both the intention-to-treat and the protocol evaluable analyses, infants fed nonacidified liquid human milk fortifier had significantly greater weight gain from study days 1 to 15 (17.9 g/kg/day vs 15.2 g/kg/day: P = .001). Infants fed with acidified liquid human milk fortifier received more protein (4.26 vs g/kg/day 4.11 g/kg/day, P = .0099) yet had lower blood urea nitrogen values (P = .010). The group fed acidified liquid human milk fortifier had more vomiting (10.3% vs 2.4%; P = .018), gastric residuals (12.8% vs 3.7%; P = .022), and metabolic acidosis (27% vs 5%; P < .001) in the intention-to-treat analysis and more abdominal distension (14.0% vs 1.7%; P = .015) in the protocol evaluable analysis. Conclusions Infants fed an acidified liquid human milk fortifier had higher rates of metabolic acidosis and poor feeding tolerance compared with infants fed a nonacidified liquid human milk fortifier. Initial weight gain was poorer with the acidified liquid human milk fortifier.

ABSTRACTObjectives:This study was a comparison of growth and tolerance in premature infants fed either standard powdered human milk fortifier (HMF) or a newly formulated concentrated liquid that contained extensively hydrolyzed protein.Methods:This was an unblinded randomized controlled multicenter noninferiority study on preterm infants receiving human milk (HM) supplemented with 2 randomly assigned HMFs, either concentrated liquid HMF containing extensively hydrolyzed protein (LE‐HMF) or a powdered intact protein HMF (PI‐HMF) as the control. The study population consisted of preterm infants ≤33 weeks who were enterally fed HM. Infants were studied from the first day of HM fortification until day 29 or hospital discharge, whichever came first.Results:A total of 147 preterm infants were enrolled. Noninferiority was observed in weight gain reported in the intent‐to‐treat (ITT) analysis was 18.2 and 17.5 g · kg−1 · day−1 for the LE‐HMF and PI‐HMF groups, respectively. In an a priori defined subgroup of strict protocol followers (n = 75), the infants fed LE‐HMF achieved greater weight over time than those fed PI‐HMF (P = 0.036). The LE‐HMF group achieved greater linear growth over time compared to the PI‐HMF (P = 0.029). The protein intake from fortified HM was significantly higher in the LE‐HMF group compared with the PI‐HMF group (3.9 vs 3.3 g · kg−1 · day−1, P < 0.0001). Both fortifiers were well tolerated with no significant differences in overall morbidity.Conclusions:Both fortifiers showed excellent weight gain (grams per kilograms per day), tolerance, and low incidence of morbidity outcomes with the infants who were strict protocol followers fed LE‐HMF having improved growth during the study. These data point to the safety and suitability of this new concentrated liquid HMF (LE‐HMF) in preterm infants. Growth with this fortifier closely matches the recent recommendations for a weight gain of >18 g · kg−1 · day−1.

BACKGROUND:Open food challenges are a practical alternative to double-blind, placebo-controlled food challenges in confirming clinical sensitivity or tolerance to a food, and the risks associated with open challenges are unknown.OBJECTIVE:To examine the safety of open food challenges administered in an office setting.METHODS:A retrospective medical record review of open food challenges, administered in a university-based pediatric allergy-immunology clinic during a 3-year period, was performed.RESULTS:A total of 109 patients (69% male) underwent 150 open food challenges, most of which were to milk (n = 39), peanut (n = 37), and egg (n = 29). There were 40 positive challenges (27% of all challenges) in 33 patients. Reactions were mild to moderate in 92% of positive challenges. Cutaneous reactions occurred in 68% of positive challenges, followed by gastrointestinal tract reactions (45%) and upper respiratory tract reactions (38%), excluding laryngeal symptoms. No patient had cardiovascular involvement. Food specific IgE values did not correlate with reaction severity. Interventions included observation or antihistamine only in 92% of positive challenges. No patient received epinephrine or required hospitalization. For negative challenges to milk, peanut, and egg, median prechallenge food specific IgE approached previously published negative predictive values for these foods. Negative challenges in patients allowed the introduction of 19 different foods into the diet of 88 patients.CONCLUSION:Open food challenges are a safe procedure in the office setting for patients selected based on history and food specific IgE approaching negative predictive values.

Belanger K, Gent JF, Triche EW, Bracken MB, Leaderer BP. Am J Respir Crit Care Med. 2006;173:297–303 PURPOSE OF THE STUDY. Chronic exposure to indoor nitrogen dioxide (NO2) may be a public health concern. The primary source of residential NO2 is gas-fueled cooking appliances. The authors’ objective was to examine associations of indoor NO2 exposure with respiratory symptoms among children with known asthma. STUDY POPULATION. Subjects were 728 children younger than 12 years with physician-diagnosed asthma living in Connecticut and southwest Massachusetts. All children had active asthma and had lived at the same address for at least 2 months before NO2 sampling. METHODS. At enrollment, a research assistant visited the home and recorded family ethnicity, housing characteristics (multifamily versus single family, number of rooms, water leaks, visible mold), presence of smoking in the home, and the use of household appliances fueled by natural gas. Mothers were also asked about number of days of respiratory symptoms experienced by the child and medications used for each month of the previous year. NO2 was measured in each home by using a Palmes tube placed in the main living area for 10 to 14 days after the enrollment visit. RESULTS. The mean concentration of indoor NO2 was 8.6 ppb in homes with electric ranges and 25.9 ppb in homes with gas stoves. The mean NO2 level measured in multifamily homes was 22.9 ppb, and the mean NO2 level in single-family homes was 10.2 ppb. Measured NO2 (>20 ppb) was associated with ethnicity: white families were least likely to have high exposures, and Hispanic families were the most likely. Among children living in multifamily housing, exposure to gas stoves and high levels of NO2 were associated with wheezing, shortness of breath, and chest tightness. For children in single-family homes, neither exposure to gas stoves nor to measured NO2 was associated with any respiratory symptom. CONCLUSIONS. The authors concluded that there is an association between exposure to high levels of indoor NO2 and respiratory symptoms in children with physician-diagnosed asthma. This association, however, was limited to children who lived in multifamily homes, probably because of the smaller size (and air volume) of the apartments. The authors also suggested a strong association of NO2 exposure with housing characteristics, lower socioeconomic status, and ethnicity. REVIEWER COMMENTS. This study demonstrated an association between increased NO2 levels and asthma symptoms of children in multifamily homes. The important potential confounders in the analysis should have been adequately dealt with in the logistic regression analysis used. The biological basis of the association is poorly understood, and the value of intervention to reduce exposure is speculative. Additional studies will be needed to clarify and confirm the association.

Wenten, M, Berhane K, Rappaport EB, et al. Am J Respir Crit Care Med. 2005;172:1563–1568 PURPOSE OF THE STUDY. To investigate the role of tumor necrosis factor (TNF) G→308A, a variant in the promoter region of TNF, that has been associated with inflammatory diseases including asthma in the susceptibility of secondhand-smoke–exposed children to respiratory illness. STUDY POPULATION. A prospective cohort of fourth-grade students (N = 1935) from 27 elementary schools in southern California from whom school-absence data were collected from January to June of 1996. Approximately 70% of the children (n = 1351) provided a buccal cell sample. METHODS. Schools provided daily absence summary information for the study subjects, and each absence was recorded as illness or nonillness. Telephone interviews regarding each illness-related absence were conducted with parents. School absences were classified as lower respiratory illnesses if wet cough, wheeze, or asthma was present. Secondhand-smoke exposure was determined by parent/guardian written responses on self-administered questionnaires and categorized as none, 1 to 29, or ≥30 cigarettes smoked per day inside the home. Asthma status was determined by parental response to the question, “Has a doctor ever diagnosed this child as having asthma?” Buccal cell samples were collected, and the genomic DNA was analyzed for the G-to-A transition polymorphism at position 308 in TNF by polymerase chain reaction and allelic discrimination assays. RESULTS. There was a 51% greater risk of lower respiratory illness–related school absences among children with secondhand-smoke exposure compared with those who were unexposed. Children with the TNF GG genotype exhibited similar absence rates regardless of whether they were exposed or unexposed to secondhand smoke. Unexposed children with at least 1 copy of the TNF G→308A allele had similar absence rates for lower respiratory illnesses compared with children with the TNF G→308GG genotype. However, absence rates in children with the variant A allele and secondhand-smoke exposure were markedly increased. Children with the variant A allele and secondhand-smoke exposure had a 75% increase in risk for illness-related absences compared with unexposed children with the GG genotype. In children with the variant A allele, illness-related absence risk increased as the number of smokers in the home increased. In addition, children with 1 variant A allele who were exposed to ≥30 cigarettes per day had a relative risk of 2.75 for respiratory illness–related school absence compared with unexposed children with the GG genotype. Restricting analysis to children without asthma did not substantially alter the findings. CONCLUSIONS. Secondhand-smoke–exposed children who carried a TNF G→308A variant allele were at highest risk for respiratory illness–related school absences. A strong dose-response relationship in this group of patients was found for respiratory illness–related absence risk in relation to the number of household smokers and number of cigarettes smoked. The genetic susceptibility associated with the TNF G→308A allele is likely mediated by variation in inflammatory responses to secondhand smoke. REVIEWER COMMENTS. Secondhand-smoke exposure is common among children and causes substantial morbidity. However, there is variation in susceptibility to the effects of secondhand smoke. This study demonstrated that differences in genotype of mediators of inflammation may explain variation in susceptibility to secondhand smoke. Additional studies are needed to elucidate differences in genotypes of other inflammatory mediators, which may produce a similar effect. This may provide one more weapon in our arsenal to convince parents to quit smoking or devise protective agents for the exposed.

OBJECTIVE. The goal was to determine whether patients seen in a referral clinic are experiencing initial allergic reactions to peanuts earlier, compared with a similar population profiled at a different medical center 10 years ago, and to investigate other changes in clinical characteristics of the patients between the 2 groups.METHODS. We reviewed the medical charts of peanut-allergic patients seen in the Duke University pediatric allergy and immunology clinic between July 2000 and April 2006.RESULTS. The median ages of first peanut exposure and reaction were 14 and 18 months, respectively; the respective ages in a similar population profiled between 1995 and 1997 were 22 and 24 months. Within our patient group, those born before 2000 were first exposed to peanuts at a median age of 19 months and reacted at a median age of 21 months, compared with first exposure at 12 months and first reaction at 14 months for those born in or after 2000. Most patients (68%) demonstrated sensitization or clinical allergy to other foods (53% to eggs, 26% to cow's milk, 20% to tree nuts, 11% to fish, 9% to shellfish, 7% to soy, 6% to wheat, and 6% to sesame seeds).CONCLUSIONS. In the past decade, the ages of first peanut exposure and reaction have declined among peanut-allergic children seen in a referral clinic. Egg allergy is very common in peanut-allergic patients, and sesame seeds should perhaps be considered one of the major food allergens. The decline in the age of first peanut reaction seems to be attributable to earlier exposure.

Purpose of the Study. Previous studies have shown that the combination of inhaled corticosteroids (ICSs) with long-acting β2 agonists improves asthma control and reduces exacerbations. The authors hypothesized that in patients already receiving daily budesonide/formoterol (B/F), replacing conventional short-acting β2 agonist (SABA) rescue with the B/F combination drug would increase antiinflammatory therapy while simultaneously giving rapid relief of symptoms. The investigators reasoned that using the B/F combination drug in this manner might reduce asthma exacerbations and improve asthma control compared with other possible regimens. Study Population. Subjects were 2760 patients with asthma (aged 4–80 years), all previously on ICSs. Methods. A double-blind parallel-group study was performed with subjects randomly assigned to 3 groups: B/F (80 mg/4.5 μg) twice daily for maintenance and also for rescue; B/F (80 mg/4.5 μg) twice daily with terbutaline 0.4 mg for rescue; or budesonide 320 μg twice daily with terbutaline 0.4 mg for rescue. Pediatric patients (11%–13% of each group) received half of the above-stated doses for maintenance. The primary outcome was time to first severe exacerbation, defined as asthma symptoms requiring an emergency department visit or hospitalization; an increase in ICS dose; use of oral steroids; or a morning peak expiratory flow rate ≤70% of baseline on 2 consecutive days. Results. Multiple positive outcomes were seen in the group using B/F for maintenance and rescue: a significant increase in the time to the first severe and mild exacerbations (P < .001); a 45% to 50% decrease in the number of severe exacerbations; significant decreases in the use of rescue medication, nighttime symptom score, and the number of nighttime awakenings; and fewer courses of oral steroids per year. The average daily dose of ICS received per patient was lower in the 2 B/F groups. All of the medications were well tolerated. Pediatric subjects receiving B/F demonstrated greater linear growth than those on higher-dose budesonide. Conclusions. Use of B/F for both maintenance and rescue is associated with a lower asthma-exacerbation rate and an improvement in several other indicators of asthma control. In addition, subjects using B/F in this manner have a decreased exposure to oral steroids and require less use of rescue medication. The authors suggest that the timing of the increase in ICS use for asthma exacerbations, rather than the total ICS dose administered, provides the greater improvement in efficacy. Reviewer Comments. The rapid onset of action of the β2-agonist formoterol suggests that it could be used as a rescue medication, although this is not a licensed indication. Use of the B/F combination as controller and rescue presents an attractive option because of the decrease in asthma morbidity compared with either B/F and SABA or ICS and SABA. Even with the use of B/F for rescue, the mean dose of ICS received was lower than in the ICS-and-SABA group (240 vs 640 μg/day in the adults) and only slightly higher than in the B/F-and-SABA group (240 vs 160 μg/day in the adults). This combination product is not yet licensed in the United States, but if approved, B/F used in this fashion will offer a novel treatment alternative for asthmatic patients. In addition, B/F maintenance and rescue therapy may provide a significant benefit for patients for whom adherence to 2 separate drugs may present serious difficulties or confusion.

Purpose of the Study. To evaluate the role of montelukast in prevention of viral-induced asthma exacerbations among 2- to 5-year-old children with a history of intermittent asthma. Study Population. A total of 549 children aged 2 to 5 years (from 68 sites in 23 countries) with a history of intermittent wheezing associated with upper respiratory infections. Methods. This was a multicenter, double-blind, parallel-group randomized trial comparing once-daily oral montelukast (4- or 5-mg chewable tablets) with placebo for 12 months. Subjects were required to have been free of symptoms and β-agonist use in a typical week over the 3 months before enrollment. An asthma exacerbation was defined as any 3 consecutive days with daytime symptoms and at least 2 β-agonist treatments per day; rescue use of oral/inhaled corticosteroids during ≥1 days; or a hospitalization because of asthma. The primary efficacy end point was number of exacerbation episodes over 1 year. Numerous secondary outcomes were also measured. Results. Patients in the montelukast group experienced a mean of 1.60 asthma-exacerbation episodes, compared with 2.34 in the placebo group, for a 31.9% rate reduction (P ≤ .001). Other end points with significant differences favoring the montelukast group included time to first exacerbation (median: 206 vs 147 days; P = .0024), rate of inhaled corticosteroid use (39.8% rate reduction; P = .027), and proportion of patients with asthma episodes (45% vs 56%; P = .008). There were no statistically significant differences in rates of oral corticosteroid use, average duration and severity of exacerbations, or proportion of patients who missed time from day care or school. Both groups experienced more exacerbations in the fall and fewer in the summer. Montelukast was well tolerated, and no patient discontinued therapy because of a drug-related adverse event. Conclusions. The authors concluded that once-daily montelukast significantly reduces asthma exacerbations secondary to respiratory tract infections compared with placebo among 2- to 5-year-old children with intermittent asthma and also reduces time to first exacerbation and need for β-agonist or inhaled corticosteroid therapy. There was no difference in severity or duration of episodes, although the authors argue that the study was not specifically designed to detect differences in these end points. Reviewer Comments. This study attempts to address the question of whether a controller medication may be useful in young children who wheeze with colds but are otherwise categorized as mild intermittent or even symptom-free. Asthma guidelines do not endorse use of preventive medications for such children, yet this study suggests that daily montelukast during the respiratory viral season may be useful to reduce exacerbations (although it did not reduce oral steroid use or severity of exacerbations). Montelukast during specified times might be a good option for many young children with intermittent asthma, but the cost/benefit ratio of chronic use is unclear, because the number of wheezing episodes per child was low even in the placebo group. Investigation of episodic use of montelukast with upper respiratory infections would be of interest.

Purpose of the Study. To determine the relationship between wheeze phenotypes in childhood and lung function at age 3 and 5 years and determine if lung function at 3 years of age predicts the development or persistence of wheeze. Study Population. A population-based cohort of 874 children from the Manchester Asthma and Allergy Study. Subjects were recruited prenatally and followed up at 3 and 5 years of age. Methods. Subjects were assigned to categories on the basis of parental report of wheezing: “no wheezing” was defined as no wheezing by age 5; “transient early wheezing” was defined as wheezing before age 3 but none in the year before the 5-year follow-up; “late-onset wheezing” was defined as no wheezing before age 3 but wheezing in the 12 months before the 5-year follow-up; and “persistent wheezing” was defined as wheezing before age 3 and in the year before the 5-year follow-up. Specific airway resistance (sRAW) was measured at age 3 and 5 by body plethysmography when subjects were symptom-free. Postbronchodilator lung function was measured as sRAW after albuterol inhalation. Results. The 530 (60.6%) subjects successfully performing sRAW at age 3 were distributed as: 248 never wheezed, 115 had transient early wheeze, 22 had late-onset wheezing, and 78 had persistent wheezing. The 730 children successfully performing sRAW at 5 years old were distributed as: 384 never wheezed, 162 had transient early wheeze, 40 had late-onset wheeze, 104 had persistent wheeze, and 40 were not classifiable. At 3 years of age, the only significant differences in sRAW between groups was an increased resistance in those with persistent wheeze compared with children with late-onset wheeze (P = .04) and those who never wheezed (P < .001). At 5 years of age, sRAW was elevated in children with persistent wheeze compared with those with transient early wheeze (P = .02) and those who never wheezed (P < .001). Also, sRAW was significantly higher in those with transient-early wheezing compared with those who never wheezed (P = .01), but there was no significant difference between those who never wheezed and those with late-onset wheezing (P = .43). Among the subgroup of children who had wheezed by age 3, the risk of persistent wheeze increased markedly with increasing sRAW values. Conclusions. Children with persistent wheeze have reduced lung function at 3 and 5 years compared with other wheeze phenotypes. In children who wheezed during the first 3 years of life, reduced lung function at age 3 predicted persistent wheezing. However, reduced lung function at age 3 did not predict late-onset wheeze in those who had not wheezed previously. Reviewer Comments. It would be useful to be able to predict whether wheezing early in life will be transient or persistent. This study augments the findings of the similarly sized, longitudinal, Tucson Children’s Respiratory Study by suggesting that (1) poor lung function at age 3 is a predictor of persistent symptoms in those with a history of early wheezing, but for individuals the measurement has limited predictive value; (2) children with transient early wheezing have increased airflow resistance at age 5 compared with those who never wheezed; and (3) those with persistent wheeze and transient early wheeze both have airflow obstruction compared with the group who never wheezed. At age 5, the group with persistent wheeze also had lower postbronchodilator lung function than the group with no wheeze, indicating that factors other than smooth muscle contraction are present early in life. Additional studies are needed to determine the factors contributing to poor lung function early in life and to identify measures that would predict persistent wheezing in individuals.

Guerra S, Lohman IC, Halonen M, Martinez FD, Wright AL. Am J Respir Crit Care Med . 2004;169:70–76 To determine if interferon γ (IFNγ) production and soluble CD14 (sCD14) levels correlate longitudinally with the risk of developing recurrent wheezing in the first year of life. Both environmental risk factors and variation in the maturation of the immune system seem to have a role in the development of asthma. Previous studies have demonstrated reduced IFNγ production in atopic and nonatopic wheezers. IFNγ production correlates positively with endotoxin exposure and with sCD14 levels, and CD14 functions as a receptor for endotoxin. Thus, …

Teper AM, Colom AJ, Kofman CD, Maffey AF, Vidaurreta SM, Bergada I. Pediatr Pulmonol . 2004;37:111–115 To evaluate the efficacy and safety of inhaled fluticasone propionate in children <2 years old with a history of recurrent wheezing and risk factors for asthma persisting into late childhood. Subjects were 30 children, aged 7 to 24 months, with ≥3 episodes of wheeze responsive to bronchodilators and a family history of asthma, allergic rhinitis, or eczema. In this double-blind study, subjects were randomized to receive either inhaled 50 μg of fluticasone twice daily, 125 μg of fluticasone twice daily, or placebo for …

Bueving HJ, Bernsen RM, de Jongste JC, et al. Am J Respir Crit Care Med. 2004;169:488–493To investigate if influenza vaccination in children with asthma prevents asthma exacerbations provoked by influenza infectionSubjects were asthmatic children aged 6 to 18 years who had no other chronic illness. There were 347 children assigned to the vaccine group and 349 assigned to the placebo group.The primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Study subjects and their families scored daily symptoms in a diary, and when symptoms reached a predefined level, a pharyngeal swab for influenza was taken. The symptom diary was maintained from the day after administration of inactivated influenza vaccine or placebo on approximately November 1 until April 1 of the following year. Secondary outcomes included the duration and severity of the asthma exacerbations, adverse effects of vaccination, and the number, duration, and severity of all asthma exacerbations. Influenza virus–specific antibody titers were measured before vaccination, 14 to 21 days afterward, and at the end of the influenza season.In each group, 344 participants provided diary data for the primary outcome. The groups were generally similar in baseline characteristics, with almost 90% of children having used maintenance medication for asthma in the previous 12 months. There were 486 reports of symptom scores that met the predefined criteria for an asthma exacerbation (vaccine group: 251; placebo group: 235), with 42 of the resultant throat swabs testing positive for influenza (vaccine group: 24; placebo group: 18). The difference in the number of asthma exacerbations was not significant (95% confidence interval: 34% reduction to 161% increase). There were no significant differences found between the 2 groups for any of the secondary outcomes measured. Antibody levels 14 to 21 days after vaccination were increased only in the vaccine group. However, when comparing the 14- to 21-day titers to those at the end of the season, ∼23% of subjects in the placebo group and 10% in the vaccine group had a fourfold increase in influenza-specific titers.The authors concluded that influenza vaccination was not more effective than placebo in reducing the number of asthma exacerbations caused by influenza infections in children.Current guidelines that recommend the use of influenza vaccination in asthmatics are based on epidemiologic evidence. A recent Cochrane review on influenza vaccination in asthmatics found insufficient evidence to make conclusions about the risks or benefits of influenza vaccination, primarily because of a lack of randomized trials. Although this study was a randomized trial, the low attack rate of influenza (∼6% of subjects tested positive by pharyngeal swab) makes it difficult to draw conclusions from the results. The study’s sample size was calculated based on the assumption of a 30% influenza attack rate, leaving it significantly underpowered to detect an effect at such a low attack rate. If the question of efficacy of influenza vaccine in reducing asthma morbidity is ever to be answered convincingly, a large randomized trial, probably over several influenza seasons, will be needed.

The safety and clinical efficacy of a liquid, β-propiolactone-stabilized intravenous γ-globulin, Intraglobin-F, was evaluated in a multicenter, double-blind study comparing Intraglobin-F to Gamimune-N, Sandoglobulin, or Gammagard. β-Propiolactone stabilizes the IgG molecule to decrease aggregate formation and is a potent virucidal agent that reduces the risk of viral transmission by intravenous γ-globulin (IVIG) preparations. Twenty-seven patients with primary immunodeficiency diseases were enrolled at three centers. Each patient received 6 months of therapy with either Intraglobin-F or the IVIG preparation that they had received during the preceding 3 months, then crossed over to the other preparation. Twenty-three patients completed the study. One patient withdrew because of an adverse event, generalized urticaria. A second patient withdrew because of fatigue and perceived decreased efficacy. Adverse reactions were comparable and occurred in 8.7% of the infusions of Intraglobin-F and 6% of the infusions with Sandoglobulin. None were severe or life-threatening. There was no discernible difference in efficacy between any of the products. The number of days when patients noted symptoms in their diaries was similar for Intraglobin-F and the comparison preparations, 4158 vs 4143. Similarly, there were no differences in the number of physician visits (33 vs 22), days missed from work or school (405 vs 404), days with fever (41 vs 47), or days of prophylactic antibiotics (675 vs 642). There was an increase in the number of days when antibiotics were given therapeutically (578 vs 451); most of the difference was attributable to one patient. There also was a difference in the number of days of hospitalization (21 vs 0), but 19 of the days were accounted for by two patients. When the patients were asked to score their feeling of well-being on a scale of 1 to 5, with 1 being entirely well, the mean score for the patients on Intraglobin-F was 1.86 (range, 1.0 to 3.0), compared to 1.85 (range, 1.0 to 3.2) for patients while on the comparison preparations. Trough IgG levels were slightly lower during the period when patients were treated with Intraglobin-F compared to the other products. There were no abnormalities in blood chemistries or hematologic parameters. Thus, Intraglobin-F is comparable to three of the marketed IVIG preparations in efficacy and safety, as well as patient acceptability, and offers the additional benefit of an extra virucidal step to reduce further the risk of transmitting viral infections.

Payne DN, Rogers AV, Adelroth E, et al. Am J Respir Crit Care Med . 2003;167:78–83 To determine whether reticular basement membrane (RBM) thickening is present among children with difficult-to-control asthma and to compare the findings with those for adults with asthma.Subjects were 19 children (6–16 years of age) with difficult-to-control asthma. Control subjects were 10 children (7–16 years of age) without asthma, 10 adults with mild asthma, 6 adults with severe asthma, and 8 healthy adults.The 19 asthmatic children underwent bronchoscopy and endobronchial biopsy as part of an asthma evaluation. Patients were treated …

Hancox RJ, Subbarao P, Kamada D, Watson RM, Hargreave FE, Inman MD. Am J Respir Crit Care Med. 2002;165:1068–1070 Tolerance to the bronchoprotective effects of β2-agonists after regular use has been demonstrated by a number of groups. These authors asked whether patients receiving scheduled β2-agonist had a decrease in response to rescue use of β2-agonist when bronchospasm is induced by a “natural” stimulus, exercise. Thus, they were looking for loss of the bronchodilator response rather than loss of protection to bronchoconstriction. Adults aged 18 to 50 years with a history of exercise-induced wheezing and a drop of forced expiratory volume in 1 second (FEV1) by at least 15% after exercise challenge. Subjects could …

Purpose of the Study. The authors used a previously generated database from the European Community Respiratory Health Survey to search for an association between childhood residence on a farm and protection from atopic disease in adult life. This investigation was prompted by the multiple studies showing decreased allergic rhinitis and asthma among children living on farms. The persistence of this effect into adult life had not been previously studied.Study Population. Patients were drawn from 48 centers in 5 countries (Belgium, France, the Netherlands, Sweden, and New Zealand). Unselected individuals 20 to 44 years old responded to a short postal questionnaire about asthma and allergy symptoms. A random sample of responders received a more extensive questionnaire and additional tests. Questions allowed identification of subjects who had grown up on a farm.Methods. Data obtained on subjects entering the second phase of the study included pulmonary function testing with methacholine challenge, total immunoglobulin E (IgE), and IgE specific for dust mite, cat, Cladosporium, and Timothy grass, and 1 additional pollen common to the region of the individual center. Subjects with farm residence in childhood were compared with those without a history of farm residence by univariate and logistic regression with adjustment for potential confounders, including pet exposure in childhood, number of siblings, and parental history of allergy.Results. Information on whether a subject had lived on a farm in childhood was available for 6251 of the 6604 subjects entering the second phase of the study. Compared with the other adults, those who had lived on a farm in childhood had a reduced risk of atopic sensitization (odds ratio = 0.76, 95% confidence interval 95% = 0.60–0.97). There was a lower risk of nasal symptoms from pollen in the farm-raised, but no difference in the prevalence of asthma compared with those not raised on a farm, or in the prevalence of nasal symptoms in the presence of animals or dust.Conclusions. The authors conclude that environmental factors encountered in childhood may have a lifelong effect on the development of allergy. The effect has been previously noted in children, but this study indicates that a reduction of allergic sensitization persists into adulthood. However, studies of children have not consistently noted a reduction of asthma in those living on farms, as indeed was not seen in these adults. The reason for the protective effect of farm residence is not clear, but several potential alternatives are not supported by the data. The effect remains even after controlling for pet exposure in childhood, number of siblings, and presence of parental allergy. Of note, the reported rate of parental allergy was similar in the farm and nonfarm parents, an argument against the “healthy farmer” effect that supposes the allergic individuals would have elected to leave the allergen-rich farm environment.Reviewer’s Comments. The hygiene hypothesis for atopy remains perplexing. Much data has accumulated in favor of the influence of early life “steering” away from atopy by environmental factors. An understanding of exactly what factors are critical or alterable remains elusive. Additionally, there is not even agreement that an effect exists for asthma, which for most patients is a much more significant illness than allergic rhinitis. For those interested, a pro/con editorial in the same journal (Am J Respir Crit Care Med. 2001;164:1106–1109) from von Mutius and Platts-Mills sets forth the arguments in more extensive fashion.