Thirty-two consecutive patients with mediastinal lesions suggestive of bronchogenic carcinoma underwent transbronchial needle aspiration. Eighteen of 20 patients (90 percent) with proved bronchogenic carcinoma had malignant cytology specimens or tissue fragments. Of 12 patients with normal cytology specimens, six were subsequently proved to have nonneoplastic disease. Transbronchial needle aspiration appears to offer a sensitive and specific alternative to more invasive surgical techniques used in the diagnosis of malignancies with mediastinal involvement.

"Ethical considerations in pulmonary genetic testing and gene therapy.." American journal of respiratory and critical care medicine, 155(1), pp. 3–8

As a clinician, I have recently received invitations from drug companies to attend all-expense-paid conferences in Paris, Nassau, Vail, and Hilton Head Island. My only obligation would be to attend one or more sessions at each conference. Drug companies continuously provide me with a generous supply of drug samples, pens and clocks. Acceptance of these is not illegal nor against my university employer's policy. These offers and gifts raise interesting and difficult questions. Is there evidence that drug companies can influence my prescribing habits? Should I accept free trips, gifts and drug samples? Are there principles to guide my decisions? Answering these questions leads physicians to confront what Albert Jonsen describes as the central paradox of medicine: the tension between self interest and altruism.1Jonsen A. Watching the doctor. N Engl J Med 1983; 308, 1531-35Google Scholar Ethical quandaries arising from physician-drug company interactions are in part due to a recent convergence of interests. As economic pressures force both academic and nonacademic physicians to adopt business-oriented practices and agreements, outcome measures (cost-benefit ratios, the bottom line) which reflect self interest rise in importance. At the same time increasingly stringent federal regulations are forcing pharmaceutical companies to risk larger sums of money, time and energy on new product development. This risk taking only further reinforces the self-interest of the industry. This convergence of economic self-interests has shifted the delicate balance in medicine away from the principles promoting altruism, and toward outcome measures which promote self-interest. Lack of resistance to this shift may be due in part to a lack of awareness of principles needed to guide physicians in their business dealings. When physicians have informal or formal contacts with drug companies, they are entering business relationships. When writing prescriptions, physicians act as surrogate consumers. When doing drug studies or agreeing to speak at meetings with honoraria subsidized by drug companies, physicians enter business agreements. It is therefore appropriate for physicians to examine principles of business ethics when trying to decide upon proper relationships with drug companies. When both medical and business ethics principles apply to a situation, it is reasonable to assume that principles of medical ethics should guide the physician because they reflect the primary obligations of physicians. Pulmonary physicians and drug companies interact in a variety of ways, the most common being the contact of the drug company representative with a physician in his or her office. But the relationships extend beyond this to include the physician as investigator, investor, owner, consultant and participant in industry-sponsored postgraduate education. It is helpful to look at these in light of existing medical and business ethics principles. All codes of medical ethics and medical organizations either directly state or imply that the patient's interest is paramount when a physician-patient encounter involves drug companies. The American Medical Association refines this by stating: “A physician may not accept any kind of payment or compensation from a drug company for prescribing its products.”2Current Opinions of the Council on Ethical and Judicial Affairs of the American Medical Association; Prepared by the Council on Ethical and Judicial Affairs. AMA, Chicago1986Google Scholar The World Medical Association International Code of Medical Ethics states: “A physician shall not permit motives of profit to influence the free and independent exercise of professional judgment on behalf of patients.”3World Medical Association International Code of Medical Ethics; amended by the 35th World Medical Assembly, Venice Italy, October, 1983Google Scholar These are reasonable statements, but they do not guide the physician when addressing the subtle business relationships which develop with drug company representatives in the physician's office. When physicians offer patients treatment, they are ideally obligated to give adequate information so that the patient can give informed consent. In the complex world of drug therapy, it is not impossible but it is impractical to give patients a course in the pertinent disciplines necessary to make their own drug choices. Rather, the physician acts as a surrogate consumer, choosing the best drug for the patient guided by the same principles of informed consent. These include adequate objective information and voluntariness. While the best sources of objective information about drugs are the peer-reviewed scientific literature, symposia sponsored by recognized medical organizations and objective drug evaluation newsletters, company representatives frequently are the physician's initial source of information about drugs. It is unlikely that drug company representatives intentionally give incorrect information; it is both illegal and not in their long-term best interest to do so. But some give carefully selected information which can be misleading.4Hemminki E Content analysis of drug detailing by pharmaceutical representatives.Med ed. 1977; 11: 210-215Crossref PubMed Scopus (30) Google Scholar There is evidence that physicians are influenced by drug companies and their sales representatives. In a Gallup poll of general practitioners, the drug company representative was rated a good or fairly good source of learning about the existence and efficacy of new products more frequently than “local clinical meetings.”5Reekie WD Weber MH Profits, politics and drugs. Holmes and Meier Publishing, New York1979: 120-127Crossref Google Scholar Furthermore, the integrity of the drug company representative is perceived as good. In a 1975 Market Investigation Survey, only 4 percent of general practitioners felt that the information given by drug representatives was distorted.5Reekie WD Weber MH Profits, politics and drugs. Holmes and Meier Publishing, New York1979: 120-127Crossref Google Scholar Yet there is disquieting evidence that physicians make drug choices based on drug company messages even when those messages conflict with scientific evidence.6Avorn J Chen M Hartley R Scientific versus commercial sources of influence on the prescribing behavior of physicians.Am J Med. 1982; 73: 4-8Abstract Full Text PDF PubMed Scopus (496) Google Scholar There is also evidence that physicians who hold these advertisingoriented beliefs generally are unaware that they are being influenced by nonscientific factors.6Avorn J Chen M Hartley R Scientific versus commercial sources of influence on the prescribing behavior of physicians.Am J Med. 1982; 73: 4-8Abstract Full Text PDF PubMed Scopus (496) Google Scholar Good decisions about drugs are best insured by avoidance of circumstances calculated to reduce voluntariness. It has been stated that giving physicians drug samples increases drug sales.7Storrs FJ Drug samples: A conflict of interest.Arch Dermatol. 1988; 124: 1283-1285Crossref PubMed Scopus (10) Google Scholar As far as I can determine, the value of giving gifts is unknown except perhaps by the industry. The statement of a former medical director of a well-known drug company suggests their value: “I have never found evidence that drug companies waste money on profitless gestures. To imply that the multibillions spent on drug advertising is spent only because an occasional doctor will be influenced into writing a prescription is not only unrealistic, it is totally illogical.”8Consale D (statement). Competitive problems in the drug industry; hearing before the Subcommittee on Monopoly of the select committee on small business, United States Senate, Part II:4495 (March 13th), 1969.Google Scholar While gifts and drug samples may be perceived by physicians as being given to demonstrate friendship, this is not the goal of the pharmaceutical industry. They are given to obtain what is perceived by the industry as fair or equal treatment or perhaps unfair advantage.9Snoeyenbos M Almeder R Humber J Business ethics. Prometheus Books, Buffalo1983: 131-134Google Scholar Accepting gifts and drug samples departs from the ethically acceptable business principle of choosing a product by rational persuasion. Rational persuasion occurs when the persuasiveness lies in the substance of the argument rather than the manner of presentation or some special relationship.10Beauchamp TL Bowie NE Ethical theory and business. Prentice-Hall, Englewood Cliffs, NJ1988: 421-430Google Scholar A sample of perfume gives the wearer relevant information about the product. Having a drug sample or gift in hand does not give a physician rational insight into the value of a drug. Gifts and drug samples are forms of manipulation which attempt to elicit a desired response from the physician by altering the availability of choices or by altering the physician's perception of choices.10Beauchamp TL Bowie NE Ethical theory and business. Prentice-Hall, Englewood Cliffs, NJ1988: 421-430Google Scholar Some have argued that drug samples and gifts are too inconsequential to affect decision-making by physicians. This may be true when one drug clearly is more beneficial than its competitors. This may not be true when several drugs have nearly identical efficacy as is often the case in a pulmonary practice. The study by Avorn et al6Avorn J Chen M Hartley R Scientific versus commercial sources of influence on the prescribing behavior of physicians.Am J Med. 1982; 73: 4-8Abstract Full Text PDF PubMed Scopus (496) Google Scholar suggests that as yet undefined factors, which may include drug samples and gifts, are instrumental in nonrational decision-making by physicians.6Avorn J Chen M Hartley R Scientific versus commercial sources of influence on the prescribing behavior of physicians.Am J Med. 1982; 73: 4-8Abstract Full Text PDF PubMed Scopus (496) Google Scholar Those who justify accepting drug samples by citing indigent patient needs fail to recognize that this is a false economy. Elimination of drug samples may benefit patients by reducing the costs of medicine by reducing drug company marketing expenses. Promotional expenditures in 1967 approximated 12.5 to 20 percent of drug company sales, significantly higher than most other industries which spent between 2 and 9 percent on marketing.11Schwartzman D Innovations in the pharmaceutical industry. Johns Hopkins Press, Baltimore1976: 203-207Google Scholar Critics also fail to recognize that this “Band-Aid” solution to providing health care for the indigent may delay a more rational and equitable solution. Public awareness of gifts and drug samples also may be detrimental to the profession. If society views these arrangements as demeaning to the profession or engendering mistrust, then gift giving and drug samples are wrong for it is not in the patients’ best interest to mistrust physicians.12Physicians and the pharmaceutical industry: American College of Physicians Position Paper.Ann Intern Med. 1990; 112: 624-626Crossref PubMed Scopus (112) Google Scholar It has been suggested by one business ethicist that the wisest policy to adopt is one of complete prohibition of any gift giving between companies and persons with whom companies do business.10Beauchamp TL Bowie NE Ethical theory and business. Prentice-Hall, Englewood Cliffs, NJ1988: 421-430Google Scholar Such a policy has recently been proposed in Great Britain by the code-of-practice committee of the Association of British Pharmaceutical Industries.13Bushe CJP Letter to the editor.N Engl J Med. 1990; 322: 65Crossref Scopus (6) Google Scholar Many Veterans Administration hospitals and armed forces medical facilities do not permit drug samples in their installations. The other common interaction that directly affects patient care is company-sponsored postgraduate educational courses. An editorial in a British Journal noted that doctors are becoming so accustomed to sponsored postgraduate education that it is difficult to attract them to meetings for which they must pay.14Rawlins MD Point of view: Doctors and the drug markers.Lancet. 1984; 2: 276-278Abstract PubMed Scopus (39) Google Scholar Yet there is some evidence that bias toward drugs manufactured by the company sponsoring the conference occurs even when these courses are given by respected academic institutions which have in place policies designed to reduce the chances of such occurrences.15Bowman MW The impact of drug company funding on the content of continuing medical education.Mobius. 1986; 6: 66-69Google Scholar Postgraduate courses with speakers and/or content selected by drug companies are potentially manipulative and therefore should be avoided. The practice of inviting physicians to attend company sponsored, all-expense-paid educational courses in attractive vacation spots extends beyond manipulation and meets the business ethics definition of bribery.9Snoeyenbos M Almeder R Humber J Business ethics. Prometheus Books, Buffalo1983: 131-134Google Scholar Bribery occurs when a physician is in the position to enhance the assets of the giver (drug company) and the gift is of a nontoken nature (a trip), such that it is reasonable to think that it may put the interests of the giver in a privileged status when all else is equal. This would not be the case if drugs were dramatically different in efficacy, but most new drugs are nearly equal in efficacy to those already on the market. While the American Surgical Association has recognized this problem and stated that physicians paid to do nothing more than to sit through symposia which are a promotional exercise are behaving unethically, physicians continue to take advantage of these free trips.16American Surgical Association. Position taken by the American Surgical Association regarding surgical ethics. Minutes; Attachment B. presented at the Annual Meeting of the American Surgical Association. Palm Beach, Florida, April 21-33, 1987Google Scholar Drug companies frequently contract with physicians to test the effectiveness of new drugs, often providing physicians with funding beyond that required to carry out the contract. Physicians may be required to set up clinical trials and solicit patient or volunteer participation to fulfill the contract. When this occurs, the physician has two obligations which may result in a conflict of interest. These are in the best interest of the patient or volunteer and the contractual obligation to the drug company. In these circumstances, the American Medical Association presents a clear and reasonable principle to be followed: “The physician must recognize that a physician-patient relationship exists … judgment and skill must be exercised in the best interest of the patient.”2Current Opinions of the Council on Ethical and Judicial Affairs of the American Medical Association; Prepared by the Council on Ethical and Judicial Affairs. AMA, Chicago1986Google Scholar One might reasonably speculate that the greater the contractual benefits for the physician, the greater the likelihood of the study participants’ interests being ignored. Concern has been voiced by a number of individuals and organizations. Both the World Health Organization and the General Medical Council of Britain have suggested that payments to investigators by drug companies should be submitted for local ethics committee review.17WHO Scientific Group. Principles for the clinical evaluation of drugs. WHO Tech Rep Ser 1968; 403Google Scholar, 18General Medical Council. Professional conduct and discipline: fitness to practice. London: General Medical Council, 1983; 27Google Scholar Any other circumstances which might reasonably alter society's trust of physicians or the physician's conscious or unconscious response to patient care also should be avoided. Thus, stock or stock options or consultative services to industry from which an investigator may subsequently profit should be avoided if the investigator is actively participating in company-sponsored research.19Special report: Conflict-of-interest guidelines for a multicenter clinical trial of treatment after coronary-artery bypass-graft surgery.N Engl J Med. 1989; 320: 949-951Crossref PubMed Scopus (45) Google Scholar On several occasions over the years I have been asked if I would be interested in speaking at symposia locally and around the country for drug companies. It is common practice for drug companies to keep a reserve of influential clinicians available to speak at hospital conferences. There is evidence that physicians who participate as speakers have the potential to influence primary care physicians, as documented in a study which showed that influential physicians can alter the practice habits of their colleagues.20Stross JK Hiss RG Watts CM Davis WK Macdonald R Continuing education in pulmonary disease for primary-care physicians.Am Rev Resp Dis. 1983; 127: 739-746PubMed Google Scholar The American Surgical Association has stated that “Giving papers or lectures at the behest of a health care industry for the primary purpose of promoting a pharmaceutical, an appliance, or any other health care supply item is not an acceptable professional service warranting remuneration.”16American Surgical Association. Position taken by the American Surgical Association regarding surgical ethics. Minutes; Attachment B. presented at the Annual Meeting of the American Surgical Association. Palm Beach, Florida, April 21-33, 1987Google Scholar Furthermore, they state that lecturers should only consider receiving remuneration if the entire program has bona fide educational character and is not primarily promotional; mentions commercial products by name incidentally or in the scientific content; if the presentation is based on valid scientific data or clinical experience; if the honorarium is proportional to work performed and travel expenses are not lavish; if they are, they should be so-stated at the symposia.16American Surgical Association. Position taken by the American Surgical Association regarding surgical ethics. Minutes; Attachment B. presented at the Annual Meeting of the American Surgical Association. Palm Beach, Florida, April 21-33, 1987Google ScholarThese seem to be reasonable criteria for speaker participation. Physicians act as consultants or buy stocks or stock options of drug companies. In these instances, when they have no other contractual obligations and no patient obligations which might be affected, principles of business ethics should guide physicians’ behavior in relationships with companies. Physicians should avoid owning stock in companies whose drugs they frequently prescribe. This is in keeping with the recommendations of the American College of Physicians.21American College of Physicians Ad Hoc Committee on Medical Ethics Ethics manual.Ann Intern Med. 1984; 101: 129-137Crossref Scopus (66) Google Scholar Is strict adherence to these principles unreasonable or excessive? Given the evidence that drug companies can influence physicians in a nonrational manner, I think not. When medical outcomes are uncertain, good will, sound medical judgment and a principled approach are all that can be asked of physicians by patients and the profession. To expand that uncertainty by making nonrational decisions and ignoring principles is not in the best interest of patients. When a physician begins to compromise his or her principles, the physician steps onto a slippery slope.

Hypocapnic constriction has been proposed as a mechanism by which collateral pathways might rapidly alter ventilation to match perfusion. We studied the changes in response to hypocapnia with age in sheep, a species with collateral resistance (Rcoll) similar to those measured in humans. Measurements of Rcoll were made with either 5 or 10% CO2 and with air (hypocapnia) in 29 anesthetized sheep, ages 6 mo to 10 yr, with the wedged bronchoscope technique. Rcoll was 0.42 +/- 0.12, 0.58 +/- 0.18, 0.32 +/- 0.18, and 0.17 +/- 0.04 (SE) cmH2O.ml-1.min in 6-mo- and 1-, 2-, and 10-yr-old animals, respectively. These values were unchanged with hypocapnia. Despite the lack of a change in Rcoll with hypocapnia, administration of histamine aerosol (8 animals) through the bronchoscope increased Rcoll by 151 +/- 35% (P less than 0.05). These data suggest that although collateral pathways exist in sheep and are capable of constriction, they do not respond to hypocapnia. Furthermore, the response to hypocapnia is not influenced by age.

We studied the effects of perfusate pH on pulmonary vascular tone, reactivity, and thromboxane and prostacyclin synthesis in isolated buffer-perfused rabbit lungs. Extracellular acidosis did not affect base-line vascular tone, but alkalosis had a biphasic effect. Increasing the perfusate pH from 7.40 to 7.65 caused vasodilation, whereas raising pH to 7.70–8.10 caused vasoconstriction. Removing calcium (Ca2+) from the perfusate completely prevented the vasoconstriction caused by alkalosis. Perfusate pH strikingly affected pulmonary vascular reactivity. Acidosis inhibited the vasoconstriction caused by thromboxane and potassium chloride (KCl) but did not affect the response to angiotensin II. Alkalosis, in contrast, augmented the vasoconstriction caused by thromboxane and angiotensin II but reduced the vasoconstriction caused by KCl. Changes in pH also altered thromboxane and prostacyclin synthesis after the infusion of exogenous arachidonic acid (AA) or the endogenous release of AA by the lipid peroxide tert-butyl hydroperoxide.

There is nothing permanent except change.

Platypnea-orthodeoxia has been described in patients with pulmonary shunts, intracardiac shunts, and severe lung disease. We report a case of platypnea-orthodeoxia in a patient with minimal obstructive lung disease and progressive autonomic failure. We have shown our patient's symptoms to be the result of an orthostatic increase in ventilation-perfusion mismatching and to be corrected with fluid challenge.

To determine the value of transbronchial needle aspiration biopsy in the diagnosis of sarcoidosis, we reviewed a 1-year experience of consecutive patients with sarcoidosis presenting with hilar and/or paratracheal adenopathy. The sensitivity of transbronchial needle aspiration biopsy in obtaining specimens of noncaseating granulomas was 90%. This yield exceeds that of most published reports of transbronchial lung biopsy and bronchial mucosal biopsy and suggests that transbronchial needle aspiration biopsy may be a valuable diagnostic tool in the evaluation of these forms of sarcoidosis.

We studied collateral ventilation as a function of age by measuring the resistance (Rcoll) and time constant (Tcoll) of collateral airflow in young (2-10 mo), mature (16-24 mo), and old sheep (6-13 yr). Rcoll was 0.50 +/- 0.11 cmH2O X ml-1 X min (SE) in young sheep and decreased significantly to 0.05 +/- 0.02 and 0.02 +/- 0.01 cmH2O X ml-1 X min in mature and old sheep, respectively. Tcoll was 34.4 +/- 7.9 (SE) s in young sheep and decreased to 5.7 +/- 0.9 and 10.2 +/- 3.1 s in mature and old sheep, respectively. We conclude that a marked decrease in Rcoll and Tcoll occurs between birth and maturity but changes little with further aging. In the young an increased resistance and time constant of collateral airflow may accentuate ventilation perfusion imbalance and impair the removal of secretions in disease states.

Lung cancer often requires an invasive surgical procedure to document inoperability. Using a fiberoptic bronchoscope with a flexible needle that can penetrate the walls of the trachea and major bronchi, we sampled mediastinal and hilar lymph nodes in 32 patients. Of 18 patients presenting with a diagnostic problem, 11 had aspirates that were positive for cancer. Surgery in 6 of the remaining 7 showed cancer in 4 (false negative). Ten other patients presented with a staging problem. Four had positive mediastinal aspirates; 3 of these 4 had a normal or equivocally normal mediastinum on chest roentgenogram. Surgery in 4 of the remaining 6 showed no cancer in 4 (true negatives). The procedure was also diagnostic in 2 of 4 patients with recurrent mediastinal small cell carcinoma and in 3 patients with intrabronchial necrotic tumors. There were no complications. We conclude that this is a safe, easily performed procedure that can replace more invasive procedures in the diagnosis and staging of lung cancer.

Although spontaneous remissions are frequent in sarcoidosis, chronic persistent disabling disease is also observed. This feature seems more frequent and more severe in black patients, as has been previously reported (10). The more extensive and severe the initial disease manifestations, the more likely it is that the disease will continue. Corticosteroids are usually beneficial and complications are infrequent. Delayed or interrupted treatment seems to allow progression or irreversible disease or both. Patient compliance is an obvious important factor. Relapses are frequent as treatment is withdrawn but are usually at least partially reversible. Some deterioration is observed with repeated relapses. Low dose daily prednisone (5-15 mg) seems to prevent relapses. Patient compliance is facilitated with daily treatment rather than alternate day therapy. Prolonged treatment for 10 to 15 or more years is often required. Chloroquine is particularly helpful in skin and mucosal disease. The necessity for long-term thoughtful management is obvious.

The role of mechanical interdependence in the perfusion of atelectatic lung was studied in two ways: a) regional hemodynamics were compared before (control) and after the development of lobar and sublobar atelectasis, and b) the effect of thoracotomy on regional hemodynamics was assessed. With lobar atelectasis mean lobar blood flow and vascular conductance decreased to 60% of control. Sublobar atelectasis caused mean sublobar blood flow and vascular conductance to decrease to 6% of control. Opening the chest after production of lobar atelectasis caused blood flow to fall to 50% of control. When sublobar atelectasis was produced in the open chest, sublobar blood flow decreased to 25% of control measurements made prior to thoracotomy. We conclude that with a closed chest, sublobar vascular distortion mediated by mechanical interdependence may be an important mechanism responsible for the differences in hemodynamic responses to atelectasis between lobes and sublobar regions.

We studied the effects of positive end expiratory pressure (PEEP) on vascular pressure flow relationships in atelectatic lobes in the closed-chest pigs and compared our results to measurements we previously obtained in sublobar atelectasis. Regional hemodynamic responses to lung inflation were significantly different between lobes and sublobar regions. PEEP caused marked increase in the fraction of cardiac output perfusing the atelectatic lobe from 16.5 +/- 2.0% (SE) to 32.5 +/- 2.0% at similar pulmonary vascular transmural pressures. In contrast, similar levels of PEEP failed to redistribute blood flow to the atelectatic sublobar regions. We propose that distortion of the sublobar region with inflation of the surrounding lung may be responsible for the failure of redistribution of pulmonary blood flow with application of PEEP.

A continuing medical education course was developed to improve the care of patients with chronic bronchitis and emphysema (COPD); 44 primary care physicians completed the course. The physicians were randomly assigned to experimental and control groups, with 3 of the 4 experimental groups assisting in the selection of topics for the programs and/or receiving feedback on tests given during the course. The course's impact was assessed using written tests to measure knowledge and simulated patient visits to observe physician performance. Experimental groups retained significantly greater amounts of information 9 months after completing the program and used more program material during patient visits than did the control group (p < 0.05). The test scores and patient visits of the 3 experimental groups involved in determining the audiovisual topics and/or receiving feedback were not significantly different from one another nor from the fourth experimental group.

In order to determine whether larger biopsy forceps improve the diagnostic yield over smaller standard forceps, we performed 30 transbronchial biopsy procedures in 28 patients with lung infiltrates using three types of instruments. We found that compared to the standard forceps specimens the large forceps acquired larger specimens in 22 of 29 procedures and that the alligator forceps acquired larger specimens in 7 of 10 procedures. However, in only 2 of the 29 procedures did the larger biopsy specimen alter the pathologic diagnosis. Four of the patients subsequently underwent open lung biopsy which did not alter the pathologic diagnosis rom the transbronchial biopsy procedure. We conclude that the large forceps do not significantly improve the diagnostic yield of transbronchial biopsy in our patients.