[Misuse of pressurized metered-dose aerosols in the treatment of bronchial diseases. Incidence and clinical consequences].
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Biomedical subjects
Publications and source records attributed to G Huchon.
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Metered-dose inhalers are the most widely-used mode of administration of bronchodilators and anti-inflammatory agents in the treatment of asthma. However, their use is complex and about 50% of the patients do not use their metered-dose inhaler(s) properly. The most frequent errors include inadequate coordination between actuation and inspiration, rapid inspiration, absence of breathhold, and actuation of the aerosol on more than one occasion during the same inspiration. The misuse of metered-dose inhalers results in a loss of efficacy of the drug. It is, therefore, recommended that the patient be carefully trained in the proper use of metered-dose inhalers at the time of prescription. If a patient is unable to use a metered-dose inhaler properly, despite education, it may be advisable to employ a different inhalation system.
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Bilateral single lung transplantation (BSLT) (the procedure of choice for double lung replacement) and single lung transplantation (SLT) have at present a low incidence of anastomotic problems. In our experience, we have recorded no death related to anastomotic problems and 4 complications occurred for 33 anastomoses with a follow up of at least 2 months. A stent was temporarily inserted for two patients. The decrease of anastomotic complications is confirmed in the literature. It is one of the reasons why the number of SLT and BSLT performed all over the world increases rapidily to the detriment of heart lung transplantation.
Aerosolization of drugs may be designed to treat lower respiratory tract and bronchial diseases and more recently infectious diseases of the lungs. The use of drug aerosol has been limited by the relative lack of knowledge about the fate of inhaled drugs. It depends on the specifications of the aerosol, the drug itself, the conditions of aerosolization, and the presence of lung disease. The advantage of the airways route is that treatment effects are obtained without systemic effects.
Thirteen single lung transplantations have been performed in our department for non-infected end-stage lung diseases. Two patients died after surgery; a female patient died of uterine carcinoma one year and six months after the operation. The remaining ten patients are alive; they have resumed an active life and often working. The number of single lung transplantation is rapidly growing in the world, whereas heart-lung transplantation is regressing considerably.
The purpose of the paper is to discuss some aspects of the methods that are most appropriate for the clinical assessment of new expectorants. Expectorants are drugs devised to help in the removal of bronchial secretions. The evaluation of these drugs is aimed at demonstrating, in controlled trials, their efficacy, safety and, if possible, mechanism of action. Unfortunately, there is no universally accepted assessment technique available. Evaluation of symptoms with the use of self-reported measures is imprecise. Studies of quality of life can assist as a means of assessing the usefulness of this class of drug for patients. Lung function tests evaluate only the possible indirect effects of expectorants; the changes observed are often minor and they do not correlate with other methods of evaluation. Mucociliary clearance studies evaluate bronchial drainage by mucociliary transport and cough. They are a useful pharmacological approach but they cannot replace therapeutic trials. In vitro and ex vivo studies of bronchial secretion, while improving knowledge of the mechanisms of bronchial secretion, fail to predict the modifications of bronchial drainage produced in vivo by cough or mucociliary transport. To be considered efficient, expectorants should not only ease the removal of bronchial secretions, but also improve the patient's condition for the duration of treatment.
In fibrosing pneumonitis, respiratory insufficiency is due to both fibrosis and inflammation induced pulmonary fibrosis. There is no treatment that can suppress fibrosis, so the current treatment of fibrosing pneumonitis--corticosteroid and/or immunosuppressive drugs--aims at reducing pulmonary inflammation and thus at slowing down the development of fibrosis which cannot regress. Therefore, it is necessary to determine the respective parts of inflammation, potentially reversible, and of fibrosis which is not. Most of the time, respiratory insufficiency cannot be prevented and requires long-term oxygen therapy. In a few patients, lung transplantation must be discussed.
Among the risk factors for chronic bronchitis and chronic obstructive lung disease, only smoking and alpha 1-antitrypsin deficiency effects have been well demonstrated. Other factors, as air pollution, occupational exposure and childhood lung diseases may have an influence, but on a lower scale. The prevention of chronic bronchitis and chronic obstructive lung disease remains mainly based on antismoking programs.
The fate of inhaled drugs depends on the specifications of the aerosol, the drug itself, the conditions of aerosolization, and the presence of lung disease. There are still many points to be elucidated before aerosols can be used more reliably in the treatment of respiratory or nonrespiratory conditions.
We measured the serum concentrations of IgG subclasses in healthy subjects (n = 26) and in patients with community-acquired pneumonia (CAP) on admission (n = 38), at recovery (n = 21), and 9 months after admission (n = 19). Then, in 8 of the control subjects and 15 of the patients, we measured IgG subclasses and mean serum antibody concentrations of pneumococcal capsular polysaccharides before and 3 wk after immunization with a pneumococcal vaccine. Compared to the control subjects, the serum concentration of the IgG2 subclass was lower at admission in patients with CAP of bacterial or unknown cause (p less than 0.005). Concentrations of IgG subclasses in patients did not differ between admission and recovery, or between admission and 9 months later. After vaccination, in both control subjects and patients, there was an increase in the concentrations of IgG2 subclasses (p = 0.01) and antipneumococcal antibodies (p less than 10(-4)). We show that serum IgG2 concentration in patients with CAP of bacterial or unknown cause is lower than in healthy subjects and remains lower for several months. After immunization with a pneumococcal vaccine, the increase in serum concentrations of IgG subclasses and antipneumococcal antibodies in patients does not differ from those in control subjects.
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To compare features of tuberculosis detected either clinically or radiologically, we studied 498 patients hospitalized for tuberculosis. Tuberculosis was less frequently radiologically-detected in patients over 65 yrs old (p less than 0.01) and in directorial staff and inactive subjects (p less than 0.0001). Pleural effusion and radiological cavities were more frequent in the symptom-detected group, but half of the radiologically-detected patients had clinical symptoms which could have led to the diagnosis of tuberculosis, especially in alcoholics and office workers. Finally, 26% of the radiologically-detected patients had positive direct tuberculosis smears and should be considered contagious.
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To determine the influence of socio-economic, clinical and radiological factors on the detection of a Mycobacterium tuberculosis-positive direct sputum smear, we studied 531 patients hospitalized for pleuropulmonary tuberculosis over a 5 year period. M. tuberculosis positivity of the expectorate smear was found more frequently in clinically detected (43%) than in radiologically detected (26%) tuberculosis (P less than 0.001). On admission, a M. tuberculosis-positive sputum smear was more common in patients under 40 years old (P less than 0.02), blacks (P less than 0.05) and alcoholics (P = 0.001). M. tuberculosis positivity on direct sputum smears was more often associated with general (asthenia, sweating, fever greater than 38 degrees C) and functional respiratory symptoms (cough and sputum production) (P less than 0.003), bilateral diffusion of lung lesions and/or excavation on chest roentgenography (P less than 0.0001). Nevertheless, 21% of the asymptomatic radiologically detected tuberculosis patients had positive direct expectorate smears and should be considered contagious.
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A case of the scimitar sign due to an anomaly of the right sided pulmonary vein with normal drainage into the left atrium was associated with an azygos continuation of the inferior vena cava. Digital subtraction angiography allows the identification of these rare congenital vascular malformations.
To investigate the mechanism of gallium-67 uptake in lung granulomatosis, we studied 13 rats in which lung granulomatosis was induced by injection of complete Freund adjuvant (CFA) and 14 controls. Gallium uptake was assessed in bronchoalveolar lavage fluid and lavaged lung. The cells responsible for gallium uptake were identified by latent image activation autoradiography. Gallium activity in both lavaged lungs and bronchoalveolar cells (BAC) was higher in CFA-treated animals than in controls [172,205 +/- 134,783 DPM versus 44,456 +/- 14,486 DPM +/- SD (p less than 0.05) and 40,083 +/- 16,350 DPM versus 9100 +/- 4114 DPM (p less than 0.05), respectively]. In control rats, about two-thirds of total lung gallium was located in the interstitium, whereas in CFA-treated rats it was found in the mononuclear cells of lung granulomas. Gallium tracks were more numerous in the alveolar macrophages (AM) of CFA-treated rats than in control AM (28.4 +/- 10.0/field versus 8.4 +/- 3.8/field, p less than 0.001) but the number of tracks was proportional to the number of AM (52.4 +/- 18.7 versus 12.2 +/- 4.3, respectively; p less than 0.001). It is concluded that in rats with CFA-induced lung granulomatosis 1) pulmonary gallium uptake increases, 2) mononuclear cells are responsible for this uptake in both granulomas and AM, and 3) the increased uptake is due to the increased number of mononuclear cells.