Hypertonic saline cough provocation test with salbutamol pre-treatment: evidence for sensorineural dysfunction in asthma.

BACKGROUND: Cough is one of the most common symptoms of asthma. However, studies using capsaicin, citric acid, or tartaric acid to document cough threshold have repeatedly failed to show statistically significant differences between asthmatic and healthy subjects. The studies using hypertonic aerosols as the cough stimulant have suggested an enhanced sensitivity in asthmatic subjects but the induced bronchoconstriction has made the interpretation of the results difficult. OBJECTIVE: To determine the cough sensitivity to hypertonicity in healthy subjects, patients with chronic cough, and patients with asthma in a setting where the induction of bronchoconstriction is prevented. METHODS: Nineteen healthy subjects, 21 non-asthmatic patients with chronic cough, and 26 asthmatic patients with chronic cough underwent an incremental hypertonic saline challenge including a pre-treatment with 0.4 mg of salbutamol. Spirometry was performed before the challenge, after salbutamol, and after the challenge. The patients with cough also underwent skin testing, histamine challenge, exhaled nitric oxide measurement, ambulatory peak flow monitoring, kept cough diary, and filled in the Leicester Cough Questionnaire. Eighteen patients repeated the saline challenge. RESULTS: The challenge did not induce bronchoconstriction in any group. The osmolality to provoke 15 cumulative coughs was significantly smaller in the asthmatic patients than in the healthy subjects (P<0.001) and in the cough patients without asthma (P=0.04). According to multivariate analysis among all the 47 patients with cough, female sex (P<0.001) and large spontaneous peak flow variation in the ambulatory recording (P=0.001) were associated with high sensitivity to saline. The saline challenge response was well repeatable (intraclass correlation coefficient 0.90). CONCLUSION: The findings of the present study are not affected by induced bronchoconstriction. Asthma or, more specifically, spontaneous, reversible airway obstruction is associated with an enhanced sensitivity to the cough-provoking effect of hypertonic saline. This suggests a pathological function of the sensorineural apparatus in this disorder.

The effects of Aspergillus fumigatus challenge on exhaled and nasal NO levels.

Several studies have previously shown that exposure to indoor air microbes from moisture-damaged buildings can cause adverse health effects. Aspergillus fumigatus is one of the best-documented moulds causing health problems to those exposed. In this study, inhalation of a commercial A. fumigatus solution was assessed, to establish if it would have effects on fractional exhaled (FeNO) and nasal (FnNO) nitric oxide levels and on lung function. The results were compared with placebo challenge. A total of 28 subjects were divided into three study groups: group 1 had been exposed to occupational mould; group 2 consisted of atopic subjects; and group 3 was a control group. Some 3 h after A. fumigatus challenge, there was a considerable increase in FeNO, and a significant difference was observed between the A. fumigatus and placebo inhalations. The difference was seen in all study groups. No such differences were found in the levels of FnNO or nitrite in nasal lavage fluid. Subjects reported significantly more frequent respiratory tract symptoms after the A. fumigatus inhalation compared with placebo challenge. In conclusion, it was shown here that inhalation challenge of Aspergillus fumigatus elevated fractional exhaled nitric oxide levels. An increase in fractional exhaled nitric oxide may serve as an indicator of respiratory inflammation of acute mould exposure.

Changes in pro-inflammatory cytokines in association with exposure to moisture-damaged building microbes.

Several epidemiological studies have described an association between adverse health effects and exposure to mould and microbes present in the indoor air of moisture-damaged buildings. However, the biochemical linkage between microbial exposure and the large variety of reported respiratory symptoms is poorly understood. In the present study, the authors compared the respiratory symptoms, the production of inflammatory mediators interleukin (IL)-1, IL-4, IL-6, tumour necrosis factor-alpha (TNF-alpha) and cell count in nasal lavage fluid and induced sputum samples of subjects working in moisture-damaged and control school buildings. The sampling was performed and the questionnaires were completed at the end of the spring term, at the end of the summer vacation (2.5 months), during the winter term and after a 1-week winter holiday. The authors found a significant elevation of IL-1, TNF-alpha and IL-6 in nasal lavage fluid and IL-6 in induced sputum during the spring term in the subjects from the moisture-damaged school building compared to the subjects from the control building. The exposed workers reported sore throat, phlegm, eye irritation, rhinitis, nasal obstruction and cough in parallel with these findings. The present data suggests an association between microbial exposure, and symptoms as well as changes in pro-inflammatory mediators detected from both the upper and lower airways.

IgG antibodies, chronic bronchitis, and pulmonary function values in farmer's lung patients and matched controls.

We measured IgG antibody levels against eight different microbes in farmer's lung (FL) patients an average of 14 years after the first diagnosed episode of FL and in matched controls. The study population consisted of 87 FL patients and 81 control farmers, matched by age, sex, and smoking habits. Clinical studies included the measurement of IgG antibody levels against Absidia corymbifera, Aspergillus umbrosus, A. fumigatus, Humicola grisea, Saccharopolyspora rectivirgula, Penicillium brevicompactum, Rhodotorula glutinis, and Thermoactinomyces vulgaris, in addition to spirometry, pulmonary diffusing capacity (DL(CO)), and the evaluation of chronic bronchitis. Median IgG antibody levels were two or more times higher in FL patients than control farmers against Ab. corymbifera, S. rectivirgula, and T. vulgaris (P<0.001). Against A. fumigatus, H. grisea, and R. glutinis, FL patients also had significantly higher antibody levels. FL patients often had positive antibody titers against several microbes, whereas control farmers usually had a positive titer against one or two microbes. A positive association between IgG antibody levels and chronic bronchitis and DL(CO) was observed in FL patients, but not in control farmers. It is suggested that the high antibody levels noted in FL patients were due not only to high exposure but also to individual sensitivity to environmental microbes.

Bone mineral density in perimenopausal women with asthma: a population-based cross-sectional study.

It is not known whether asthma constitutes a risk factor for osteoporosis or what the impact is of inhaled corticosteroids on bone mineral density (BMD). The study population (n = 3,222) was a random stratified sample from the Kuopio Osteoporosis Study, which included all women 47 to 56 yr of age residing in Kuopio Province, Eastern Finland. Spinal and femoral BMDs were measured using dual-energy X-ray absorptiometry. The BMD values of 119 asthmatics were cross-sectionally compared with those of 3,103 nonasthmatics. Of the 119 asthmatic women, 28 had not used corticosteroids, 65 had used oral corticosteroids, and 26 had used only inhaled corticosteroids. The asthmatics with no hormone replacement therapy (HRT) (n = 83) had lower mean spinal and femoral BMD value than did the corresponding nonasthmatics (spinal BMD, 1.083 +/- 0.150 [SD] versus 1.128 +/- 0.160 g/cm2, p < 0.05; femoral BMD, 0.894 +/- 0.112 [SD] versus 0.929 +/- 0.128 g/cm2, p < 0.05). Although BMDs were not significantly decreased in the asthmatics who had used inhaled corticosteroids, the duration of use correlated negatively with spinal BMD and was also associated with spinal BMD in multiple regression analysis. In perimenopausal women, asthma is associated with decreased bone density. This may be due to the corticosteroids rather than to the disease itself. However, HRT appears to be protective against bone loss also in asthmatics.

Long-term risk of emphysema in patients with farmer's lung and matched control farmers.

We evaluated the long-term outcome of farmer's lung (FL) patients and matched control farmers using high-resolution computed tomography (HRCT). The study population consisted of 88 FL patients and 83 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yr. The great majority, 82%, of the studied subjects were nonsmokers. Clinical studies included HRCT, spirometry, and pulmonary diffusing capacity. Emphysema was found significantly more often (23%) in FL patients than in control farmers (7%) (p = 0.006). The presence of emphysema was 18% in nonsmoking and 44% in smoking FL patients, the respective values being 4% and 20% in control farmers. Patients with recurrent attacks of FL tended to have emphysema more often (p = 0. 08) than patients who had experienced only a single attack. Fibrosis was observed in 17% of the FL patients and in 10% of the control farmers (p = 0.2). Miliary changes were found in 12% of the FL patients compared with 4% of the control farmers (p = 0.07). Both emphysematous and fibrotic but not miliary changes correlated significantly with impaired pulmonary function. In conclusion, farmer's lung disease seems to be associated with an increased risk of developing emphysema.

Powered dust respirator helmets in the prevention of occupational asthma among farmers.

OBJECTIVES: This study investigated the value of powered dust respirator helmets in the treatment of farmers with occupational asthma. METHODS: The study population consisted of 33 asthmatic agricultural workers, 24 with occupational asthma induced by cow dander or grains, 2 with other forms of atopic asthma, and 7 with nonatopic asthma. The efficiency of a powered dust respirator helmet with a P2-class filter in preventing asthmatic symptoms was assessed for 1 year. Morning and evening peak expiratory flow rates and daily symptoms of the subjects were monitored for 3 months without the use of the helmet and for 10 months with the helmet. RESULTS: Objective evidence of protection was obtained for farmers with occupational asthma. The morning peak flow rate increased and the variation in daily peak flow rate and the symptoms of cow-barn rhinitis diminished significantly during the helmet period. In the group of farmers with nonatopic asthma there was no improvement in peak flow rate or symptoms of asthma, although some of these farmers also seemed to benefit from helmet use. CONCLUSIONS: The results of this study suggest that especially dairy farmers with occupational asthma benefit from the use of a powered dust respirator helmet.

Long-term outcome of pulmonary function in farmer's lung: a 14 year follow-up with matched controls.

The long-term outcome of pulmonary function was evaluated in farmer's lung (FL) patients compared to representative control farmers. This is, to our knowledge, the first such study which has included a control group. Clinical examinations were conducted in 89 FL patients and 84 control farmers, matched by age, sex, and smoking habits. The mean time after the first diagnosed episode of FL was 14 yrs. The mean transfer factor of the lung for carbon monoxide (TL,CO) was on average 12% lower (p < 0.001) in FL patients compared to control farmers. In spirometry, the mean maximum expiratory flow at 50% of vital capacity (MEF50) was lower (p = 0.08) in FL patients but there were no differences in mean vital capacity (VC) or forced expiratory volume in one second (FEV1) between FL patients and control farmers. However, airway obstruction, defined as an FEV1/VC less than 88% of predicted, was more common in FL patients than in control farmers (33 versus 17%; p = 0.02). Patients who had had recurrent episodes of FL had a significantly lower mean TL,CO compared to those FL patients who had experienced only a single episode. In conclusion, impairment of the pulmonary transfer factor is the most important long-term consequence of farmer's lung. However, farmer's lung may also lead to development of airway obstruction.

The diagnostic value of cold air hyperventilation in adults with suspected asthma.

The diagnostic value of isocapnic hyperventilation of cold air (IHCA) is not fully established. All 342 adult patients in whom IHCA had been performed because of a clinical suspicion of asthma between 1992 and 1994 were analysed retrospectively in the authors' hospital. In addition, 26 healthy subjects were recruited. According to strict criteria, the patients were divided into asthmatics and symptomatic non-asthmatics. For the calculations of sensitivity, specificity and accuracy, the symptomatic non-asthmatic group served as a control. The post-test probability of asthma after IHCA was determined for all the possible pre-test probabilities by applying Bayes' theorem. A linear regression model was used to investigate the factors associated with the reactivity to IHCA. A single 4-min IHCA and skin prick tests were performed in the healthy subjects. Of the 287 patients in the final analysis, 113 were defined as asthmatics and 174 as symptomatic non-asthmatics. The accuracy was highest using a 9.0% fall in forced expiratory volume in 1 s (FEV1) as a cut-off value; the specificity was then 86.8% and the sensitivity 31.9%. The authors found IHCA to be a useful diagnostic test only if the pre-test probability of asthma is between 0.30 and 0.56. The positive final diagnostic gain of IHCA is 22% at its best, but the negative gain is negligible for all possible pre-test probabilities. Factors associated with reactivity to IHCA were young age and, to a lesser extent, a history of cold-weather-associated respiratory symptoms and pre-challenge bronchial obstruction. If a rigid cut-off value for a positive response is used in all age groups, the specificity of IHCA is good but the sensitivity is unacceptably low in adults. The diagnostic value of IHCA might increase if age is taken into account when defining the cut-off value.

Asthma in patients with farmer's lung during a five-year follow-up.

OBJECTIVES: This study assessed the incidence of asthma in patients with farmer's lung. METHODS: The study population consisted of 1031 patients who had occupational farmer's lung diagnosed from 1983 to 1988. The cases of farmer's lung were registered in the nationwide Register of Occupational Diseases by the Finnish Institute of Occupational Health, and all the patients in the study had received compensation from the insurance company for an occupational disease. The diagnosis of asthma was based on entitlement to a special refund for asthma medication costs from the national sickness insurance program. RESULTS: Seventy-four cases of asthma were found among farmers with farmer's lung up to the end of the 5 years following the year of the diagnosis for farmer's lung. The prevalence of asthma was 1% in the year preceding the diagnosis. In the year of the diagnosis and during the 5 year of follow-up, asthma was diagnosed in an additional 6% of the patients. CONCLUSIONS: The results of this study confirm previous findings of a low prevalence of asthma before the onset of farmer's lung in small groups of patients. However, the results also indicate that the incidence of asthma increases during the first years after an episode of farmers lung. For example, in the present study, asthma was apparent in 7% of the patients 5 years after the diagnosis of farmer's lung.

Recovery of pulmonary function in farmer's lung. A five-year follow-up study.

The recovery of pulmonary function in farmer's lung (FL) was studied during a 5-yr follow-up in 101 patients (20 men and 81 women, mean age 47 yr). At the initial evaluation all patients had the first diagnosed attack of FL. Spirometry, measurement of pulmonary diffusing capacity, and arterial blood gas analysis were done at the time of the diagnosis and 1, 3, 6, 12, and 24 months thereafter. The last follow-up measurements were made 4 to 6 yr after the initial evaluation. Mean FVC improved significantly for up to 1 yr. In mean DLCO there was improvement for up to 2 yr. Mean PaO2 rose to its maximum within 1 month of the initial examination and did not change significantly thereafter. No patient had diagnosed asthma at the time of the diagnosis of FL, but asthma was later diagnosed in 7 patients during the follow-up. In conclusion, the pulmonary function of FL patients improved for up to 2 yr after the initial acute episode. In general, PaO2 improved most rapidly; the improvement in FVC was slower, and the recovery of DLCO took the longest time.

Effect of corticosteroid treatment on the recovery of pulmonary function in farmer's lung.

The effect of corticosteroid treatment on the course of farmer's lung (FL) was studied in 36 patients randomly allocated in a double-blind placebo-controlled study. All patients were in the acute stage of the disease and had had the first diagnosed attack of FL. Twenty patients were given prednisolone treatment for 8 wk. Sixteen patients received an 8-wk placebo treatment. One patient was withdrawn from the analysis when she terminated corticosteroid treatment because of side effects. After 1 month of treatment there was a significant difference (p = 0.03) in DLCO between the treatment groups. After a follow-up of 5 yr no statistically significant differences were found between the treatment groups in FVC, FEV1, or DLCO. FL recurred in six patients during the follow-up in the corticosteroid group and in one patient in the placebo group, but the difference was not statistically significant. In conclusion, in the corticosteroid group the improvement of pulmonary function was more rapid than in the placebo group, but no influence on the long-term result was found. The possibility that corticosteroid treatment may favor the occurrence of recurrent attacks of FL needs attention.