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.

Effect of farming environment on sensitisation to allergens continues after childhood.

AIMS: The farming environment in childhood has been reported to decrease the risk of sensitisation to allergens. The purpose of the present study was to explore whether later exposure to a farming environment also could affect this sensitisation. METHODS: A population based sample of 202 women who did not live on a farm and 231 who did. The subjects filled in a questionnaire and underwent skin prick tests for several common and farming related allergens. RESULTS: The prevalence of sensitisation to any of the allergens was similar in the two groups (37.1 v 34.6% (p = NS). However, compared with women who did not live on a farm, the women who lived on a dairy farm showed a low prevalence of sensitisation to pollens (4.4 v 17.3%, p = 0.01) and cats (3.5 v 10.4%, p = 0.047). The risk of sensitisation to pollens and pets was lowest among women with both a childhood and adulthood farming environment and was dose dependently associated with current contact with farm animals. However, this contact increased the risk of sensitisation to bovine dander. CONCLUSION: The farming environment may reduce sensitisation to common allergens also after early childhood. However, it may also increase sensitisation to farm allergens.

Allergen-specific sensitization in asthma and allergic diseases in children: the study on farmers' and non-farmers' children.

BACKGROUND: Farmers' children are less frequently sensitized to common allergens than the non-farmers' children, but less is known about their sensitization to other allergens and its association with clinical diseases. OBJECTIVE: To examine the association of farm environment with atopic sensitization, allergic diseases, expression of allergen-induced symptoms, and the importance of specific sensitization against 'common' (timothy, dog, cat, birch, Dermatophagoides pteronyssimus, mugwort) and 'other' (cockroach, horse, Lepidoglyphus destructor, cow) allergens for asthma and allergic diseases in children. METHODS: A cross-sectional study including 344 farmers' and 366 non-farmers' children aged 6-13 years in eastern Finland, using a self-administered written questionnaire and skin prick tests against the above-mentioned allergens. RESULTS: Farmers' children had less asthma and allergic diseases and were less often sensitized against common allergens than the non-farmers' children. However, little difference was observed in sensitization against the other allergens between the farmers' (17.2%) and non-farmers (14.5%) children [adjusted odds ratios (aOR) 1.11 (0.71-1.72)]. Being sensitized against only other allergens, without sensitization against common allergens, was unrelated to asthma or allergic diseases. Among the single allergens, sensitization against pets or pollen, or against horse or cow, had the strongest association with asthma, hayfever, and atopic eczema; no such association was seen in D. pteronyssimus, mugwort, cockroach, or L. destructor. Farmers' children had significantly less often symptoms of allergic rhinitis in contact with dog (aOR 0.32%, 95% confidence interval (CI) 0.15-0.67), cat (aOR 0.45, 0.22-0.88), or pollen (aOR 0.58%, 95% CI 0.37-0.90) than the non-farmers' children. CONCLUSION: Farm environment reduces the occurrence of asthma, allergic diseases, and atopic sensitization in children, and also the occurrence of allergen-induced rhinitis. Remarkable differences were observed between single allergens in their association with allergic disease, stressing the importance of allergen selection when defining atopy in epidemiological studies.

Pet- and pollen-induced upper airway symptoms in farmers and in nonfarmers.

The effect of farming on the risk of upper airway symptoms is not clear. In this cross-sectional, population-based study, 198 female farmers, 50 nonfarmers living on a farm, and 218 nonfarmers not living on a farm, filled in a symptom questionnaire and underwent skin-prick testing with common and agricultural allergens. In the logistic regression analysis, the latter group served as a control. Several adjustments were made, including childhood farming environment. Current farming was found to decrease the risks of pet- and pollen-induced upper airway symptoms, dose-dependently with the intensity and duration of animal husbandry. Including skin-test positivity to pets in the regression models did not affect the negative association between farming and pet-induced symptoms. In contrast, animal husbandry increased the risk of farm work-induced upper airway symptoms. Animal husbandry often induces work-related upper airway symptoms. However, the present study among female adults suggests that it may also decrease the risk of pet- and pollen-induced upper airway symptoms.

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.

Bronchoconstriction due to cold weather in COPD. The roles of direct airway effects and cutaneous reflex mechanisms.

To clarify how cold weather may induce bronchoconstriction in patients with COPD, a series of challenges were performed in 20 patients with COPD in stable condition as well as in 13 healthy subjects. A whole-body exposure to -17 degrees C during resting nasal breathing was performed to study the reflex effects of facial cooling on lung function. In addition, a near-maximal hyperventilation of cold air was performed in a warm room to study the direct airway effects of cold air. The whole-body exposure to cold air induced statistically significant bronchoconstriction in both groups, the maximal decrements in FEV1 being 9.4 +/- 1.4% in the patients with COPD and 10.3 +/- 0.8% in the healthy subjects (p = NS). The whole-body exposure to cold air also increased the resting ventilation. The hyperventilation challenge induced bronchoconstriction only in the patients with COPD, the maximal decrements in FEV1 being 8.0 +/- 1.3% and 1.5 +/- 1.0%, respectively (p < 0.01). These results suggest that cooling of the facial skin is predominantly responsible for the bronchoconstriction due to cold weather both in patients with COPD and in healthy subjects. At high ventilation level, as during heavy exercise, the direct airway effects of cold air may also contribute to the bronchoconstriction in patients with COPD. Some patients with severe COPD might benefit from wearing protective clothing over their face in cold weather.