Mucus hypersecretion (greater than 25 ml/day) is commonly seen in chronic bronchitis, whereas bronchorrhea (greater than 100 ml/day) is found in other conditions (e.g. asthma, bronchiectasis, alveolar-cell carcinoma). Clearance of secretions can be improved by physical and pharmacological methods. Cough airways obstruction--for "two-phase air-liquid flow". Chest physiotherapy (the forced expiration technique, FET, and postural drainage, PD) is effective in clearing central and peripheral secretions and can be self-employed. Oral high frequency oscillation (OHFO) at 13 Hz is a useful adjunct. Beta-adrenergic drugs improve clearance and this is not entirely to their bronchodilator activity. Likewise methylxanthines enhance clearance particularly in central airways. Corticosteroids are effective in bronchorrhoea and asthma. Anticholinergics may control hypersecretion. Mucolytics and expectorants are used traditionally but their activity is difficult to prove. Hypertonic (7%) saline is useful--as is cromoglycate in asthma.
The aim of this series of studies was to investigate the quality and quantity of farmers' exposure to airborne spores during the handling of hay or grain. In the beginning, the Petri dish method and later a six-stage Andersen sampler were used to collect the samples. The number of spores of mesophilic fungi, thermotolerant fungi, thermophilic actinomycetes and fungi of the Aspergillus glaucus group were determined in order to find possible causative agents of farmer's lung disease. The level of exposure varied from 10(4) cfu/m3 to 10(7) cfu/m3 (cfu = colony forming unit). In hay, fungi of the A. glaucus group usually dominated. In grain the most common moulds were Cladosporium spp. and Penicillium spp. In both hay and grain the most common thermophilic actinomycete was Thermoactinomyces vulgaris; Micropolyspora faeni was found less frequently. Silaging was found to be the best method to prevent moulding of hay. Chemicals added during baling did not satisfactorily prevent moulding of hay. For stored grain, however, the best results were obtained with propionic acid treatment. The quality and quantity of airborne spores found suggests that farm work exposes farmers to a high risk of becoming sensitized, which leads to the development of asthma or farmer's lung. Few of the methods presently available for making or storing hay and grain can satisfactorily prevent moulding. So far, use of personal dust respirators with a type P2 (previously II b) filter seems to be the only way to effectively diminish exposure to spores.
In order to compare the prevalences of common allergic symptoms identical postal questionnaires were sent to all farmers of a rural municipality in eastern Finland and to a sample of similar size in the adjacent industrialized urban municipality. To investigate the validity of the survey random subsamples of each study group participated in health examinations. In both the rural and urban populations subjects most frequently suffered from allergic rhinitis, 26.7% and 28.8%, respectively of the two populations. The proportions of individuals with any one of the five allergic symptoms recorded did not differ significantly in the two populations. Asthma was somewhat more frequent among the urban than among the rural population. The difference was not statistically significant, however, and could be due to the difference in smoking habits. The factors reported to provoke allergic symptoms were significantly different in the two groups. In the rural population the provoking factors were mostly work-related, whereas in the urban population these factors were related to living conditions.
Tracheobronchial mucociliary clearance was measured in 37 patients with early simple chronic bronchitis. A non-invasive radio-aerosol technique with inhalation of 99Tcm labelled 5-microns polystyrene particles followed by assessment of radio-nuclide distribution by posterior gamma-camera scans was employed. The mucociliary clearance of the bronchitics was significantly lower than clearance of a non-smoker control group. An interim analysis of the effect of treatment with a surfactant stimulating drug, ambroxol, suggested a dosage-dependent tendency to a faster mucociliary clearance than seen in placebo-treated bronchitics.
Nasal fluid is a heterogeneous substance. It consists largely of a secretory product derived from the 100,000 small seromucous glands. The anterior part of the nose has a relatively high secretory capacity, but this does not seem to be caused by secretion from the 200 anterior serous glands. Compared to sputum, nasal secretion has a lower viscosity, but comparable spinability; it has a lower dry weight, and content of sulphate, sugars and most proteins, but a comparable level of albumin. Watery rhinorrhoea is mainly reflex-mediated. Watery, but not purulent nasal discharge can be reduced by the cholinoceptor antagonist, ipratropium, administered in a dose which matches the degree of the symptoms. It seems likely that the nose, in some respects, can serve as a model for the analysis of airway secretions, but a comparative study of nasal and of bronchial secretions sampled in an identical way is warranted.
Seventeen victims of farmer's lung were monitored during two indoor feeding seasons for cattle. The victims, who had all recovered from the acute phase of the disease before entering the experiment, used powered helmets for respiratory protection (Air-Stream) equipped with Type P2 filters. Filters were changed once a week. The lung function of each subject was investigated at the beginning and towards the end of the indoor feeding season. Each subject kept a diary about the use of dust respirators, changing of filters, inconvenience related to the use of respirators, and symptoms experienced during the follow-up. None of the subjects reported symptoms they related to farmer's lung, and mean values for the lung function parameters (PEF, FEV1, FVC, DLCO, and KCO) did not decrease during the two follow-up periods. In contrast, mean DLCO and KCO increased slightly. At the very end of the both indoor feeding seasons, after the actual follow-up periods, one subject developed mild recurrences of the disease without deterioration detectable by radiology. The patient asserted that he had used the protective helmet properly. The results indicate that powered respirator helmets have protective value in farmer's lung and are appropriate for long-term use. A possibility remains, however, that the disease may recur in highly sensitized individuals, despite the use of efficient protective devices. Other measures for preventing or decreasing mould exposure are equally important.
In dairy farmers exposed to the microbes present in hay, precipitating antibodies against these microbes are frequently found regardless of the state of health of the farmer. The prognostic value of these antibodies for the future health and working ability of farmers was studied in a six-year follow-up survey of 292 farmers. During these six years, of the farmers aged 45-59 years in the primary survey, 14 men (22%) and 15 women (22%) had retired or changed occupation because of illness. Among the men, the presence of precipitins was negatively correlated with their working ability reported in the follow-up study. The risk of occupationally disabling respiratory disease was three times higher in men with precipitins against microbes present in mouldy hay than in precipitin-negative farmers of the same age. No similar correlation was found for women.
A postal survey was used to investigate the characteristics of farmers who have acquired dust respirators. In 1979 about a quarter of the farmers were using dust respirators, men more often than women. The more vocational training the farmer had and the larger the area of land under cultivation the more likely he was to own a dust respirator. Grain producers had purchased the protective devices more frequently than other farmers had. Farmers who participated in the occupational health intervention during 1980-82 had acquired dust respirators considerably more often than those in the control group. In the intervention group men under 30 years had most frequently purchased the dust respirators. Participation in the intervention influenced the acquisition of dust respirators more than did occurrence of symptoms of chronic bronchitis or farmer's lung.
Work-related respiratory diseases are common among farmers. Few studies, however, have dealt with the consequences of respiratory diseases for the lives of the afflicted farmers. To estimate the socioeconomic consequences of respiratory diseases in the farming population, we made a cross-sectional study and a follow-up study. In 1979 farmers with farmer's lung were twice as likely as healthy farmers to plan to reduce their farming work or to stop farming completely. Fifteen percent of the farmers who developed chronic bronchitis during a three-year follow-up had decided to reduce farming work, close down the farm or change the line of production on the farm. The respective rate for healthy farmers was 8%. In 1982, after the follow-up study of new cases of respiratory diseases, the rate of giving up occupational activities was twice as great among individuals with farmer's lung or asthma as in the rest of the farming population. Based on this study, we estimated that of the new cases of respiratory diseases, every tenth will stop farming in the near future, owing to one of the respiratory diseases analyzed. In Finland about 300 farmers per 100,000 and a total of about 600 farmers annually reduce their farming work or stop farming due to respiratory diseases.
Increased pulmonary proteolytic (elastolytic) activity is thought to be the primary cause of emphysema and may also play a rôle in the pathology of bronchitis. These diseases are common amongst tobacco smokers. Serum-derived alpha 1-proteinase inhibitor (alpha 1PI) and locally produced protease inhibitors normally protect the pulmonary epithelium from proteolytic attack, but tobacco smoke can inactivate these antiproteases by oxidative and non-oxidative mechanisms. Bronchoalveolar lavage fluid (BALF) samples lung surface components and most studies show that there is elevated elastolytic activity in smokers' BALF. Whether antiproteolytic capacity is reduced in these samples remains debatable. A selective lavage technique is described which independently samples central and peripheral epithelium from the same subject. Analysis demonstrates a protease-antiprotease imbalance which can differ in central and peripheral lavage and which could be significant in the development of obstructive airways disease. Therapeutic approaches include augmenting antiprotease potential using genetically engineered, oxidant-resistant alpha 1PI or synthetic peptide inhibitors.
Density gradient ultracentrifugation has been used to analyse the lavage from the proximal intrapulmonary bronchi of normal human volunteers and of dogs. The secretion from explants of canine trachea and human lobar bronchi has been examined under basal conditions and after stimulation by secretagogues. Mucus from the hypersecretory airways has been obtained from tracheostomized patients and from a canine model of chronic bronchitis produced by exposure to SO2 gas. No macromolecule of density gradient typical of an epithelial glycoprotein was recovered from normal basal secretions: the glycoconjugate recovered was of higher density and has sugars typical of a proteoglycan. The explant produced typical epithelial glycoprotein if stimulated. As volume of secretion increases, macromolecular yield does also, both of epithelial glycoprotein and of a number of lipids that are synthesised by the airway and which are different from alveolar lipids.
Monoclonal antibody based immunohistochemistry is a very powerful tool for the establishment of a pathological diagnosis of lung cancer. Applying a panel of intermediate filament antisera and an antibody recognizing neuroendocrine differentiation we have tested about 240 human lung tumors and 15 human lung tumor cell lines. Our results can be summarized as follows: a differential diagnosis between neuroendocrine and non-neuroendocrine lung tumors can be obtained by the application of the monoclonal antibody MOC-1 directed against neuroendocrine antigens. Immunohistochemistry can lead to a better recognition of lung tumor heterogeneity within the established histologies. Examples of this phenomenon are: the presence of neuroendocrine and/or neural components within non-neuroendocrine tumors. The presence of squamous cell or adenocarcinomatous differentiation in non-SCLC can be detected by chain specific anti-cytokeratin antibodies. The degree of differentiation towards the variant type within SCLC can be detected by the monoclonal antibody directed against neurofilaments. lung cancer cell lines can serve as an in vitro model for immunohistochemical studies on different lung cancer subtypes.
The pharmacologic treatment of cough can be divided into two main categories: therapy with controls, prevents or eliminates cough (i.e., antitussive) and therapy that makes cough more effective (i.e., pro-tussive). Definitive antitussive therapy depends on determining the aetiology or operant pathophysiologic mechanism and then initiating specific treatment; it can be almost uniformly successful. Non-specific antitussive therapy is directed at the symptom; it is indicated when definitive therapy cannot be given. For pathologic cough in man, predominantly studied in patients with chronic bronchitis, the following non-specific antitussive drugs have been shown to be effective: aerosolized ipratropium bromide, all narcotics of the phenanthrene alkaloid group (e.g., morphine and codeine), and the non-narcotics, dextromethorphan, glaucine, diphenhydramine, caramiphen, viminol and diviminol. Although studies have shown that hypertonic saline aerosol can improve cough clearance, there are no data, to date, that have convincingly demonstrated this agent or any other pro-tussive drug to be clinically useful.
The prenatal and postnatal therapeutic management of surfactant insufficiency are reviewed. Prenatal maternal glucocorticoid therapy promotes lung maturation and enhances lung surfactant levels in the neonate, but a minimum of 24 hr treatment is required and the therapy is of limited effectiveness even under optimal conditions. Relatively few women in premature labour are good candidates for glucocorticoid therapy. Research into combinations of glucocorticoids with hormones (e.g. thyroid), and adrenergic agents in progress. The authors are studying the effects of fibroblast-pneumonocyte factor (FPF) on the fetal lung surfactant system. Postnatal therapy with insufflated natural and artificial surfactants has been studied in several centres with varying degrees of success. Currently, the risk:benefit ratios favour attempts to reduce the risks of respiratory distress syndrome (RDS) by both prenatal surfactant induction and postnatal replacement therapy. Greater understanding of the underlying mechanisms should permit the establishment of more satisfactory treatment.
Excessive bronchial secretions within the airways can be transported by two-phase gas-liquid flow with airflow rates encountered during normal tidal breathing. The transport speed of secretions with this mechanism is as effective as the mucus clearance rate in normal subjects. The thickness of bronchial secretions required to effect two-phase gas-liquid flow is about 10% of the airways diameter which is not an unusual situation for patients who have bronchial hypersecretion. Periodic airflow as encountered in normal breathing is more effective than continuous flow in moving secretions in one direction or another. However, to propel the secretions toward the larynx, expiratory airflow velocity should be higher than inspiratory airflow velocity. This pattern can be achieved by imposing a controlled pattern of mechanical ventilation and is also probably the basis for the "huffing manoeuvre" taught by chest physiotherapists to clear airway secretions. Increased elasticity and decreased viscosity of secretions promote higher transport rates by two-phase gas-liquid flow. Conditions for two-phase gas-liquid flow during tidal breathing can be met at the 8th to 9th generation of the airways.
Prevalence and incidence of chronic bronchitis and farmer's lung in the Finnish farming population were studied by cross-sectional and follow-up surveys of 12,056 farmers. Occurrence of both these diseases varied greatly according to geographical location of the farm. The incidence of chronic bronchitis (2,687 new cases annually per 100,000 farmers) was twice as large in southwestern as in northern Finland. Chronic bronchitis was more common among farmers in livestock production than among those in grain production. The definition of farmer's lung adopted confined the occurrence of the disease among farmers engaged in animal tending. In livestock production, chronic bronchitis was strongly associated with swine tending, but farmer's lung with both cattle and swine tending. Use of a harvester with a sack loader turned out to be characteristic of the chronic bronchitis cases, and the number of new cases was largest among farmers who used a batch type cell drier. The farmers with grain driers that use unheated air most frequently suffered from farmer's lung. Of all (147) the characteristics of farming occupation analyzed, the methods of grain handling and drying were the most important factors for predisposing farmers to chronic bronchitis and farmer's lung.
