Inhaled bronchodilator's in asthma: low or high dose?

We studied the effect of regular inhalations of low-dose and high-dose fenoterol and low-dose and high-dose combinations of fenoterol and ipratropium bromide in maintenance treatment of 120 adults with moderately severe asthma. We used a double-blind, randomized, parallel group design comparing 12 weeks of treatment with four regimens: fenoterol, 100 micrograms/dose; fenoterol, 200 micrograms/dose; fenoterol, 50 micrograms; and ipratropium, 20 micrograms/dose in a single inhaler (Berodual) and fenoterol, 100 micrograms and ipratropium, 40 micrograms/dose in a single inhaler (Duovent). During the baseline and active treatment period the patients recorded PEFR in the morning and evening, symptoms and use of a rescue inhaler. Changes in twice daily peak expiratory flow rates or asthma symptoms did not show any significant differences among the four treatment regimens during the 12 weeks compared with the baseline period. Use of the rescue inhaler did not differ among the four groups during the active treatment. The patients' assessment of the efficacy of the active treatment favored the low-dose fenoterol and low-dose combination. More side effects were recorded in the high-dose combination group during the first 4 weeks compared with the other groups. We conclude that in maintenance therapy of chronic asthma high doses of fenoterol alone or in combination with ipratropium bromide offer no clinical advantage over low doses. On the contrary, the low-dose fenoterol and the low-dose combination are better accepted and tolerated by the patients.

Farmer's lung--a 5-year follow-up of eighty-six patients.

We studied the clinical course of eighty-six patients with farmer's lung for a period of 5 years. The patients were first evaluated at an acute or sub-acute stage of the disease and 1, 3, 6, 12 and 60 months thereafter. Special attention was paid to the development of lung function and radiological findings with reference to corticosteroid treatment and antigen contact during the follow-up. Many of the patients were severely ill at the acute stage of the disease. Most of the recovery took place during the first month. Significant improvement of lung function happened up to 6 months, thereafter the improvement was insignificant. After 5 years, respiratory symptoms were reported by 65% and minor respiratory dysfunction (lowered diffusing capacity) was observed in about 40% of the farmers. Thirty-two per cent of the patients showed diffuse opacities in chest X-ray. Corticosteroid treatment had no effect on long term prognosis. There was no difference in the recovery of lung function between those who returned to work compared with those who did not. Exacerbations happened in 8% of the patients during the follow-up. We conclude that respiratory symptoms, minor airway dysfunction and mild radiological fibrosis are common findings after 5 years of an acute or sub-acute stage of the farmer's lung. However, in Finland two-thirds of the patients return back to their previous occupation of farming and cattle feeding.

Radiologic findings in farmer's lung. Prognosis and correlation to lung function.

We classified the radiologic findings of 93 patients with acute or subacute farmer's lung (FL) disease by type and severity of the change in chest x-ray film. Acute radiologic changes, further divided as nodular, ground-glass, or striated patchy opacities, were found in 78/93 patients at the first evaluation; 11 showed chronic changes (radiologic "fibrosis"), which persisted unchanged throughout the follow-up period; and four initially had a normal chest x-ray film. Patients were followed up 23 months on an average. The more severe the radiologic change at the first evaluation, the more impaired the diffusing capacity (Dsb). Severe radiologic changes disappeared more slowly than the less severe ones. The differences in the initial pulmonary function values between the two groups disappeared during the follow-up. The type of acute change did not predict the recovery of respiratory performance. Treatment with oral corticosteroids did not affect the outcome of lung function or appearance of chronic changes, although corticosteroids seemed to hasten the disappearance of diffuse opacities. At the final evaluation, the chest x-ray film was normal in 55/93 patients. Chronic changes were detected in 38 patients. Severe radiologic appearance and striated patchy opacities predisposed to development of chronic changes.

Clinical aspects of farmer's lung: airway reactivity, treatment and prognosis.

This study reviews the results of five clinical studies dealing with farmer's lung (FL). The total number of patients included was 107, with a mean age of 49 years. All patients were farmers with dairy cattle. The clinical symptoms, auscultatory findings, chest radiography, laboratory data, partial pressure of oxygen in arterial blood at rest (PaO2), dynamic spirometry (FVC and FEV1) and lung diffusing capacity of carbon monoxide (DLco) were recorded at the first visit to the hospital and one, three, six and twelve months later during the follow-up and every six months after that. Half of the patients with FL reported insidious onset of the disease, and 28% reported acute onset. Dyspnoea was reported by all patients, coughing was almost as common. A considerable proportion of the patients reported muscle and joint pains. Diffuse opacities were detected in the chest radiograms of 99 patients (93%): the more severe the radiological change, the more impaired the DLco value. A normal chest radiogram was seen in eight of the 107 patients at the first evaluation. Half of the patients showed a restrictive type of impairment of ventilatory function at the first evaluation. Lung diffusing capacity was less than 80% of the predicted value in 89% of the patients. Ninety-nine patients were initially challenged with histamine and twenty-two of them (22%) showed increased bronchial responsiveness. Bronchial hyper-reactivity was transient in most of the patients and might also fluctuate with exacerbation of FL symptoms. Specimens of the airway epithelium of FL patients were taken by rigid bronchoscope from five patients for electronmicroscope studies. Extensive bronchial damage to the airway epithelium associated with the presence of spore-like fungi was observed. Aspiration biopsy of the spleen was carried out on ten FL patients during their first visit to the hospital. Granuloma-like reactions were detected in the aspiration biopsy material of five FL patients. The granulomatous changes in the spleen had disappeared when the procedure was repeated on two patients at an asymptomatic stage of the disease. Ninety-three patients were included in a follow-up study with a mean follow-up period of 18.6 months. The patients with clinically less severe disease were observed without medication. It appeared that corticosteroid medication was usually started if the DLco value was less than 65% of the predicted value. Fourteen patients with a DLco value less than 65% were observed without medication and served as a control group for those on medication.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of corticosteroid treatment on the course of farmer's lung.

In this prospective study of farmer's lung disease 93 patients were subjected to a follow-up period of an average of 18.6 months. The patients were initially divided into three groups, each receiving corticosteroids either for four weeks, twelve weeks, or not at all, if the disease was less severe. Lung function, clinical findings and chest radiography were recorded at intervals of one, three, six and 12 months and every six months after that. Corticosteroid treatment seemed to have no marked influence on the course of lung function or the prognosis of working capacity. Twelve-week treatment did not produce better results than four-week. However, corticosteroids diminished the appearance of fibrotic changes in chest radiograms. It is concluded that corticosteroids should be given to severely ill patients to ameliorate symptoms, but no apparent benefit is derived from long-term treatment. Eighty-five per cent of patients continued farming and cattle-feeding after recovery. The severity of the initial attack and the occurrence of relapses were found to be the most important factors influencing respiratory performance, subjective symptoms and working capacity in patients with farmer's lung.

An electron-microscopic study of the airways in patients with farmer's lung.

By electron-microscopy, we have shown that airway epithelial changes occur in farmer's lung, at a level which is even as high as the carina of the right upper lobe. When spores were apparent in the bronchial lumen, ciliated and goblet cells had disappeared, and in some specimens, even basal cell layers. In general, the ciliated cells were those most affected; the cell destruction is that of bronchitis, with the cilia being less affected than the rest of the ciliated cell. Ciliogenesis is stimulated but it does not keep pace with the cell destruction, which advances more rapidly. Disturbed ciliogenesis is suggested. The pathogenesis of epithelial damage is obscure. By reason of epithelial damage, it is suggested that the superficial afferent nerves in the bronchial epithelium are susceptible to irritation; degranulating mast cells in the vicinity of the epithelial nerves may also be involved in the bronchial hyperreactivity observed in some patients. Mast cells were found in the alveoli; these might influence alveolar ventilation. The alveoli presented granulomas characteristic of farmer's lung.