Portal de Periódicos da CAPES

IPPB in COPD

1984; Elsevier BV; Volume: 86; Issue: 3 Linguagem: Inglês

10.1378/chest.86.3.341

1931-3543

NULL AUTHOR_ID,

Inhalation and Respiratory Drug Delivery

Intermittent positive pressure breathing (IPPB) therapy for lung diseases was first recommended about 30 years ago, and ever since has been the subject of controversy of varying intensity. In particular, the use of IPPB in chronic obstructive lung disease (COPD) has excited interest, because of the expense of the therapy and the magnitude of the COPD problem. Though most careful studies of IPPB in COPD produced negative results, it was the belief of the participants in the “Sugarloaf Conference” of 19741Pierce AK Saltzman HA Proceedings of the conference on the scientific basis of respiratory therapy.Am Rev Respir Dis. 1974; 110 (part 2) Chairmen.Google Scholar that the then-available evidence was not conclusive and that a formal clinical trial was warranted. The Division of Lung Diseases (DLD) of the National Heart, Lung and Blood Institute took this advice and made funds available for such a trial to be carried out by a number of centers working under research contracts. Five clinical centers (Baylor College of Medicine, University of California at San Francisco, University of Oklahoma, Loma Linda University and University of Manitoba) and one data center (George Washington University) were selected in open competition, and investigators from these centers met to work out a common, detailed protocol for the trial using general guidelines from DLD. This was successfully achieved,2National Heart, Lung and Blood Institute, Division of Lung Diseases. Protocol for intermittent positive pressure breathing program. National Institutes of Health, Bethesda, Maryland1978Google Scholar and in 1977, patient enrollment began. About 1,000 patients with COPD were recruited who were without severe hypoxemia or other serious disease, and who were available for intensive long-term follow-up. Patients underwent extensive baseline testing, including studies of lung function, exercise capacity and psychologic status, and were then randomly assigned either to IPPB or to treatment with a compressor nebulizer (CN). Both machines supplied the patient with nebulized bronchodilator drugs and both were to be used in the same way; the difference between treatments was that one machine applied positive pressure to the lungs and the other did not. Both groups were also treated with a standard regimen which included the usual therapies given to North American patients with COPD. Patients were followed-up intensively for three years. They were visited at monthly intervals by a nurse-practitioner who checked their clinical status and their compliance with treatment. Baseline tests were repeated at regular intervals. All results were reported to the data center, which checked and analyzed them. The trials progress was monitored by an expert advisory group, interim results not being available to the clinical centers. The results of this trial have recently become available and can be summarized as being strongly negative.3IPPB Trial Group Intermittent positive pressure breathing therapy of chronic obstructive pulmonary disease: a clinical trial.Ann Intern Med. 1983; 99: 612-620Crossref PubMed Scopus (147) Google Scholar At baseline, the IPPB and CN groups were well matched in terms of a host of characteristics. Over the three-year follow-up, the two groups showed similar death rates, and similar figures for number and duration of hospitalizations. Changes in life quality as objectively assessed did not differ between the two groups. Lung function, while showing significant deterioration in both the IPPB and CN groups, changed a similar amount in each. In an effort to delineate subgroups showing a therapeutic effect, patients were separated according to degree of airways obstruction, reversibility of obstruction, sputum production, and the probability of emphysema. In none of these subgroups was IPPB a significantly better treatment than CN. These results may be regarded as definitive in showing that the regular application of positive pressure to the lungs of stable patients with COPD is of minimal or no therapeutic value. Obviously, the results cannot be applied with any confidence to situations other than those which were under study. For example, extrapolation of these data to patients with nonobstructive lung disease is unjustified, and more important, the results of the trial cannot be used to condemn IPPB as a therapeutic maneuver in COPD patients who are acutely ill. It might be argued that the trial results should not be applied to patients with COPD who are hypoxemic, but during the trial IPPB patients who became hypoxemic did not fare better than those receiving CN, and the close similarity of mortality results argues against a benefit in patients with more severe disease. A major question concerning the interpretation of the trial results revolves around how one should interpret the results in the “control” group receiving CN therapy. Should the course of these patients be regarded as representative of that experienced by COPD patients in general, or not? Has IPPB been shown to be no better than the usual treatment of COPD or just no better than a special and perhaps beneficial alternative? Given the nature of the clinical trial, these questions cannot be answered with certainty, but some inferences can be drawn regarding likely answers. First, the trial demanded close follow-up of the patients and in this respect the treatment of both groups probably differed from the “usual” therapy of COPD. No study emphasizing the continuous accumulation of accurate data from sick patients can avoid involving the patients in an intense, focused medical care system; making the required measurements may well have altered that which was measured. Second, in spite of the above, compliance with both CN and IPPB therapy was disappointing. Though patients were asked, told, and exhorted to use their machines at least 30 minutes per day, only about 55 percent of them used their machine for 25 minutes or more per day. In view of the efforts made to ensure adherence to treatment, this level of success may represent the maximum obtainable. The presence in the trial of a large number of patients who were not compliant with either treatment did afford the opportunity to examine whether outcome was related to compliance. It did not appear to be; patients who did not use either treatment did no worse than patients who did. This result suggests that neither treatment was of benefit, but cannot be regarded as definitive since patients who complied could not be assumed to be a random sample of patients under study. Those who did not comply with treatment may have done so in reaction to treatment and their reaction might have related to whether the treatment was IPPB or CN, thereby biasing analyses of outcome according to compliance. Though bias cannot be conclusively shown to have been absent, there was no evidence that machine use differed according to which machine was assigned to a given patient. Thus, the most plausible interpretation of the fact that non-compliant patients did as well as compliant ones is that neither CN nor IPPB therapy was of benefit. Thus, it is likely that any difference which may exist in outcome between the patients in the trial and COPD patients in the community at large is due to the intensity of the follow-up of trial patients and not to the use of CN or IPPB. Use of IPPB as a treatment in out-patients with COPD can no longer be justified. It is not clear what the implications of this finding are in terms of future physician behavior, even if it is assumed that physicians behave in a rational manner, because it is not known how widespread this form of treatment is at present. It has been suggested that between 1974, when the clinical trial was conceived, and 1983, when it was completed, the use of out-patient IPPB therapy had decreased to the extent that very little remains to be discontinued. This hypothesis cannot be tested, but it is probably true that current use of IPPB varies widely in North America, and is less prevalent in academic centers than in non-academic milieus. Whatever the direct impact of the clinical trial of IPPB on patient care, a great deal should be learned from it. A very large group of very well characterized patients were observed very closely for a substantial time. The result is a vast library of data bearing on the characteristics and course of COPD. Appropriate exploitation of these data should materially advance our understanding of this syndrome. This is the next task of the IPPB Trial Group, and we invite the participation and advice of the pulmonary community.