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Asthma, Exercise-Induced↗
Biomedical subjects
O Löwhagen
Publications and source records attributed to O Löwhagen.
Allergen specific immunotherapy attenuates early and late phase reactions in lower airways of birch pollen asthmatic patients: a double blind placebo-controlled study.
BACKGROUND: Few placebo-controlled studies have examined the effect of allergen specific immunotherapy (SIT) on early and late phase asthmatic reactions. In this placebo-controlled study we have investigated the effect of 1 year of SIT with standardized birch pollen extract on early and late phase asthmatic reactions in adult asthmatic patients. METHODS: Nineteen patients with a history of birch-pollen-induced seasonal symptoms from upper and lower airways, positive skin prick test and in vitro specific immunoglobulin E to birch pollen extract were included. Allergen and methacholine bronchial challenges were performed and blood samples obtained for analyses of total eosinophil count and eosinophil cationic protein (ECP) in serum, before and after 1 year of immunotherapy treatment. RESULTS: All patients developed early and 16 of 19 both early and late phase asthmatic reactions. A significant increase in allergen dose was required to evoke early asthmatic reaction in the immunotherapy group (P < 0.01) after 1 year of treatment. The difference between the groups was significant (P < 0.01). Also the size of late asthmatic reaction was significantly reduced in the SIT group compared with placebo treated patients (P < 0.01). Twenty-four hours after allergen challenge methacholine sensitivity, number of total eosinophils and ECP increased significantly in the placebo (P < 0.02, P < 0.05 and P < 0.05 respectively), but not in the SIT group. CONCLUSION: Allergen SIT with standardized birch pollen extract decreased early and late asthmatic responses following bronchial challenge in pollen allergic patients, thus confirming anti-inflammatory effect of the treatment.
Adult↗
Haplotypes of the interleukin-4 receptor alpha chain gene associate with susceptibility to and severity of atopic asthma.
BACKGROUND: Development of asthma is likely to depend on a complex interaction between environmental and genetic factors. Several groups have suggested the gene of the IL-4 receptor alpha chain (IL4R) as a candidate gene for the development of asthma, although association with single polymorphisms has shown contradicting results. OBJECTIVE: We chose to analyse IL4R gene haplotypes and assess their possible relevance in susceptibility to asthma and to certain clinical phenotypes. METHODS: IL4R gene haplotypes were analysed, based on the three markers C-3223T, Q551R and I50V, using the expectation-maximization algorithm, in 170 atopic asthma patients and 350 controls, all adult Swedish Caucasians. RESULTS: Our data showed significantly higher levels of soluble IL-4R (sIL-4R) in asthma patients compared with controls (P<0.0001). Furthermore, we showed a significant association between the IL4R haplotype containing the alleles T-3223, V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a frequency of 6.5% in the patients compared with 1% in the controls (P<0.0005). A subgroup of patients with heterozygous or homozygous state for the T-3223, V50 and R551 alleles, also had lower levels of sIL-4R in their circulation compared with patients with homozygous state in the C-3223, I50 and Q551 alleles (P<0.05) and showed less severe asthma according to lung function test (P<0.05). Analysis of single markers showed the T-3223 IL4R allele to associate with lower serum levels of sIL-4 receptor (P<0.0001) and patients carrying the T allele also had more symptoms of active asthma (wheezing, P<0.01; coughing, P<0.05 and breathing difficulties, P<0.01). CONCLUSION: Our data suggest that asthmatic patients with low levels of sIL-4 receptor may represent a genetically distinct subgroup of atopic asthma. TVR haplotype analyses confirm the importance of IL4R as a candidate gene for susceptibility to asthma. This finding may have implications for the understanding of the pathogenesis of asthma and possibly for the development of more specific therapies.
Adolescent↗
Sensitivity to methacholine and capsaicin in patients with unclear respiratory symptoms.
BACKGROUND: Capsaicin, the pungent ingredient in red pepper, is known to stimulate coughing via the sensory nervous system. Earlier studies showed that patients with airway symptoms induced by chemicals and strong scents cough more after inhalation of capsaicin than healthy control subjects and this has been interpreted as a hyperreactivity of airway sensory nerves. Our aim was to study airway sensitivity to inhaled capsaicin and the occurrence of airway symptoms induced by strong scents in patients who underwent a bronchial methacholine test, primarily because of suspected asthma. METHODS: Fifty-two consecutive patients referred for testing with methacholine were also provoked with inhaled capsaicin in increasing concentrations. Cough sensitivity to capsaicin was compared with that in 40 healthy control subjects. RESULTS: The patients coughed significantly more compared with the healthy control subjects with each dose of capsaicin (P < 0.0001). Twelve patients (23%) had a positive methacholine test, and of these, nine were diagnosed with asthma. There was no difference in capsaicin sensitivity between patients sensitive or insensitive to methacholine. CONCLUSIONS: The majority of the patients had no increased sensitivity to methacholine but did demonstrate sensory hyperreactivity (SHR). SHR appears to be a common diagnosis in investigations of patients with obscure airway symptoms.
Adolescent↗
Increased nasal mucosal swelling in subjects with asthma.
OBJECTIVE: The objective of this study was to evaluate nasal mucosal swelling with acoustic rhinometry in subjects with asthma and in healthy controls. METHODS: We examined 184 individuals with asthma and compared with 156 randomly selected controls outside the pollen season, where 144 subjects in the asthma group and 80 controls had a previous history of non-infectious rhinitis (NIR). Nasal mucosal swelling was assessed with acoustic rhinometry before and after nasal decongestion with oxymetazoline and was analysed for the crosssectional area (4cm from the nostril) and the volume between 3.3 and 4cm from the nostril. Symptom scores for nasal blockage, secretion, itching and sneezing were assessed on a 0-10 visual analogue scale as well as peak nasal inspiratory flow and spirometry. RESULTS: Before decongestion there was a decrease in the cross-sectional area at 4 cm (1.32 cm2 vs. 1.59 cm2, mean left + right P = 0.04) and in the volume (1.70 vs. 1.91 cm3 P = 0.03) in the asthma group compared with healthy controls. After decongestion there were no significant differences in cross-sectional area at 4cm (1.66 vs. 1.73cm2 P=0.32) or volume (2.12 vs. 2.24cm3 P=0.32). Combined nasal symptom scores were higher in the asthma group (1.8 vs. 0.8, P=0.0001) and peak nasal inspiratory flow was lower (119 vs. 124 L/min, P = 0.38) than the healthy controls. FEV1 (% predicted) was also lower in asthma group (84 vs. 93% P < 0.0001). CONCLUSION: We have been able to demonstrate an increased nasal mucosal swelling in a population sample of persons with asthma compared to healthy controls. These data support previous reports of a generalized airway inflammation in patients with asthma and suggest that acoustic rhinometry can be used to monitor the nasal mucosal swelling in these patients.
Adult↗
The inflammatory marker serum eosinophil cationic protein (ECP) compared with PEF as a tool to decide inhaled corticosteroid dose in asthmatic patients.
The objective of this study was to compare the inflammatory marker eosinophil cationic protein (ECP) with peak expiratory flow (PEF) in determining the therapeutic needs of inhaled corticosteroids in asthma patients assessed as asthma symptoms. A randomized, single-blind study over 6 months was performed at six specialist centres in Europe. In total, 164 adult patients with moderate to severe symptomatic asthma and regular use of inhaled corticosteroids were included. After a run-in period of 2 weeks patients were randomly allocated to the ECP or the PEF monitoring group. The dose of inhaled cort costeroids was adjusted every fourth week based on the current serum ECP value or pre-bronchodilator morning PEF values as surrogate markers of therapeutic needs. At the end of the study there were no statistically significant differences in the mean daily symptom score or the percentage of symptom-free days between the two groups. The mean daily dose of inhaled corticosteroids was similar in the two groups at the start of the study but the algorithms used to adjust the dose of inhaled corticosteroids resulted in an increased use of inhaled corticosteroids in both groups. The mean daily dose of inhaled corticosteroids over the whole study period was significantly lower in the ECP group compared withthe PEF group (1246 vs. 1667 microg, P = 0.026). In the ECP group, forced expiratory volume in I sec (FEV)% predicted was lower at the end ofthe study compared with the begining (92% vs. 87%, P = 0 .0009), although there was no significant difference between the two groups. None of the used algorithms for ECP and PEF led to improvement in symptom scores, in spite of increased doses of inhaled corticosteroids. In this respect, both methods were equivalent and insufficient. Recommendations suggesting lung function tests in current guidelines may be difficult to translate into clinical practice, however, a combination of inflammatory markers, lung function and symptoms may still improve asthma control.
Administration, Inhalation↗
Differences in trigger factors and symptoms between patients with asthma-like symptoms and patients with asthma: development of a basis for a questionnaire.
Patients with asthma-like symptoms but with negative asthmatests are often misdiagnosed as having asthma and treated as asthmatics. They describe their trigger factors and symptoms very similar to those of patients with asthma. The aim of the study was to analyze differences in symptoms and trigger factors between asthma-like patients and asthmatics in order to elaborate a basis for a questionnaire for epidemiological and clinical use. A questionnaire with 54 questions about trigger factors and 137 questions about symptoms was sent to 40 patients with asthma-like symptoms and 40 with asthma, all consecutively selected from patients referred to an out-patient clinic for asthma and allergy for investigation of suspected asthma. Data were analyzed statistically in two steps using multiple logistic regression analysis. Significant differences were seen in several trigger factors and symptoms after the first analysis. After the second analysis, seven out of the 54 trigger factors and 22 out of the 137 symptoms emerged as those that most significantly discriminated between the two patient groups. These trigger factors and symptoms can be the basis of a new questionnaire with high discriminating power. Before using it, it is important to evaluate the best combination of variables, add some demographic variables and totestthe reliability and validity ofthis new questionnaire.
Adult↗
Capsaicin inhalation test for identification of sensory hyperreactivity.
BACKGROUND: Patients with upper and lower airway symptoms and with pronounced sensitivity to chemical odours, such as perfumes, flower scents and tobacco smoke, have been suggested to have sensory hyperreactivity (SHR). The symptoms have been difficult to identify with physiological measurements and the effects of various medications are doubtful. However, these patients have been found to be more sensitive to inhalation of capsaicin than healthy people. The aim of this study was to establish limit values with the capsaicin inhalation test in patients with SHR. METHODS: Ninety-five consecutive patients with upper and lower airway problems, who were admitted for allergy testing, underwent a capsaicin inhalation test with three different concentrations. The number of coughs was registered during each challenge. Score systems were used for symptoms and influence on social life of sensitivity to odours. In relation to scored symptoms, the patients were grouped as SHR or not, and compared with 73 healthy controls. RESULTS: All patients and controls coughed on capsaicin in a dose-dependent manner. Symptom score of odour sensitivity in patients was positively correlated to the response of the test. Out of 95 patients, 15 (16%) were scored to SHR. Patients with SHR reacted more to the capsaicin inhalation test than the other patients and the healthy controls. The limit values for a positive capsaicin inhalation test for the SHR were determined to be 10, 35 and 55 coughs at 0.4, 2.0 and 10 microM capsaicin, respectively. CONCLUSION: The capsaicin inhalation test well reflects the degree of airway sensitivity to chemicals and to what extent the social life is influenced. The cut-off values of the test can distinguish patients with pronounced sensitivity to odours.
Administration, Inhalation↗
Asthma and asthma-like disorder, a 5-year follow-up study.
Consecutive adult patients (n = 70) referred for investigation of suspected asthma were reinvestigated after 5 years with the same diagnostic procedures (airway symptom score, spirometry, methacholine test) as used at the initial investigation. The same diagnostic criteria for asthma, asthma-like disorder (current asthma-like symptoms but negative asthmatests)and chronicobstructive pulmonary disease (COPD) were used at both visits. At the first visit 39/70 patients (56%) fulfilled the asthma criteria, 21/70 (27%) fulfilled the asthma-like criteria and 5/70 (7%) the COPD criteria. Due to lack of current symptoms 5/70 (7%) could not be classified. 5/70 patients (7%) were smokers, however, in the majority (72%) smoke was not tolerated as it induced asthma-like symptoms. At the investigation, 5 years later, 30/39 patients (76%) still fulfilled the asthma criteria and 12/21 patients (57%) still fulfilled the asthma-like criteria. At the 5-year investigation, 10% of patients in the asthma group now fulfilled the asthma-like criteria and 10% of patients in the asthma-like group fulfilled the asthma criteria. It is concluded that asthma as well an asthma-like syndrome may persist for 5 years or more. It is also concluded thatthe two disorders are closely related as patients in the asthma group over time could move into the diagnostic criteria ofthe asthma-like disorder and vice versa.
Adolescent↗
Recruitment of CD1a+ Langerhans cells to the nasal mucosa in seasonal allergic rhinitis and effects of topical corticosteroid therapy.
BACKGROUND: Local antigen presentation may be necessary for both primary and recall T-cell responses to grass pollen in hay fever patients. We examined the effect of seasonal allergen exposure on nasal mucosal antigen-presenting cell (APC) populations and the effects of topical corticosteroid therapy. METHODS: Nasal biopsies were collected from 46 grass pollen-sensitive seasonal rhinitis patients before the grass-pollen season. A second biopsy was collected during the pollen season, when patients had received 6 weeks' treatment with either fluticasone propionate (200 microg, twice daily) or placebo. Cell populations in biopsy sections were quantified by immunocytochemistry. RESULTS: Significant increases in submucosal and epithelial CD1a+ Langerhans cells, but not CD68 + macrophages or CD20 + B cells, were observed during the pollen season. Seasonal increases in CD1a+ Langerhans cells were inhibited by corticosteroid therapy. CONCLUSIONS: Recruitment of CD1a+ Langerhans cells to the nasal mucosa during natural seasonal allergen exposure may contribute to local T cell responses. Topical corticosteroids may act, at least in part, by inhibiting effective allergen presentation to T cells through inhibition of recruitment of Langerhans cells to the nasal mucosa.
Administration, Topical↗
Quality of life and capsaicin sensitivity in patients with sensory airway hyperreactivity.
BACKGROUND: A group of patients with asthma-like symptoms and sensitivity to chemical irritants has shown an increased cough sensitivity to inhaled capsaicin compared to patients with asthma and to healthy controls. The condition is called sensory hyperreactivity (SHR), and the patients often feel that they are socially handicapped because of the risk of exposure to chemical irritants in daily life. METHODS: Twenty-six patients with asthma-like symptoms after exposure to nonspecific irritating stimuli, but without IgE-mediated allergy or demonstrable bronchial obstruction, were selected for a study of the response to a capsaicin test and measurement of quality of life by a general health profile (the Nottingham Health Profile [NHP]). We also investigated whether there was a correlation between quality of life and sensitivity to capsaicin. RESULTS: The patients demonstrated a dose-dependent response to the capsaicin provocation, with coughing and respiratory and other symptoms, that significantly differed from 12 healthy controls. The health profile showed that patients with SHR had a significantly reduced quality of life compared to reference values, and there was a significant correlation between the health profile and sensitivity to capsaicin. CONCLUSIONS: Patients with asthma-like symptoms verified by the capsaicin inhalation test for sensory hyperreactivity have a poor quality of life. The correlation between quality of life and sensitivity to capsaicin objectively demonstrates the validity of this general health profile study.
Administration, Inhalation↗
Combining a beta2-agonist with a face mask to prevent exercise-induced bronchoconstriction.
BACKGROUND: In this study, we aimed to test the effect of combining a P2-agonist with a heat- and moisture-exchanging cellulose face mask in patients with bronchoconstriction induced by exercise in cold air. METHODS: Nine allergic, asthmatic patients with a history of adverse reaction to exercise were tested on an ergometric bicycle at a temperature of approximately -10 degrees C. They were in turn given no treatment, given premedication with a beta2-agonist, allowed to breathe through a heat- and moisture-exchanging cellulose face mask, and given both premedication and the face mask. After each treatment regimen, they were subjected to provocation with exercise and cold air. RESULTS: The decrease in FEV, was greatest with no therapy (mean maximal change: 27%), and this diminished when the face mask was used (mean maximal change: 12%,) or premedication with a 32-agonist was given (mean maximal change: 7%); no decrease in FEV1 occurred with the combination of agonist and face mask. CONCLUSIONS: The results suggest that different mechanisms are involved in the pathophysiology of exercise-induced bronchoconstriction (EIB). This finding may be of importance for asthmatic athletes who train and compete in a cold climate and are affected by small changes in their lung function.
Adrenergic beta-2 Receptor Agonists↗
Exercise-induced respiratory symptoms are not always asthma.
Eighty-eight patients with a history of exercise-induced respiratory symptoms performed a maximal exercise test in order to study the reasons for stopping the test. There was a wide range of percentage maximal fall in peak expiratory flow (PEF), from minus 3% to 63%, mean 11%, recorded 0-30 min, mean 12 min after the break. In the controls the maximal decrease was 0-16%, mean 6%. Diagnostic criteria for asthma were fulfilled by 48 patients (55%). Of these patients 42% had a fall in PEF > or = 15% (exercise-induced asthma). Of the non-asthma patients 10% had a fall > or = 15%. The most common reason for stopping the exercise in the asthma group was breathing troubles (46%), the most common reason in the non-asthma group was chest pain/discomfort (35%). In about 20% of the patients dizziness and/or pricking sensations in arms or legs indicated hyperventilation as an additional reason for stopping the exercise. It is concluded that other kinds of reaction, than bronchial obstruction such as breathing troubles not directly related to bronchial obstruction and chest pain, may be important factors that can restrict physical capacity in patients with exercise-induced respiratory symptoms.
Adolescent↗
Asthma and asthma-like disorders.
Bronchial asthma is defined as a chronic inflammatory disease resulting in a reversible and variable bronchial obstruction. For the clinical diagnosis of the disease there are some key indicators but as there is no 'gold standard' a correct diagnosis will sometimes not be obtained. Examples are patients in a symptom-free stage, current medication interfering with the methods used, patients with asthma-like symptoms reporting lack of effect of bronchodilators and patients who are unable to perform a forced expiration in an airway function test. The prevalence of asthma is reported to be 5-10%. The prevalence of asthma-like symptoms may be double this. The term 'asthma-like' has been used to an increasing extent during the last few years, which may indicate an increasing awareness of the fact that asthma-like symptoms are not always classical asthma. In this overview some disorders with asthma-like symptoms, especially in adults, are presented. The spectrum of differential diagnoses in a clinic may depend on which doctor/specialist the patient is consulting. In an asthma and allergy clinic it has been found that the most common differential diagnoses are chronic obstructive pulmonary disease (COPD), nonasthmatic cough and sensory hyper-reactivity (SHR), a disorder which is sometimes mixed up with asthma due to similar symptoms (heavy breathing, cough, increased secretion, difficulty in getting air etc.) and similar trigger factors (smoke, strong scents, exercise, cold air etc.). Recently it has been suggested that a capsaicin inhalation test may be an objective test for identifying patients with SHR. In asthma effective treatment is available today but in asthma-like disorders, such as SHR, no effective therapy is available, underlining the need of further research for understanding the pathophysiological mechanisms.
Asthma↗
Provocations with perfume in the eyes induce airway symptoms in patients with sensory hyperreactivity.
BACKGROUND: In earlier studies, we have shown that patients with a history of sensory hyperreactivity develop asthma-like symptoms when exposed to strong scents, even if they cannot smell any scent. METHODS: For study of possible pathophysiologic mechanisms behind sensory hyperreactivity, the patients' airways and eyes were separately exposed to a common inducing factor, perfume. Eleven patients with a history of hyperreactivity to chemical trigger factors, such as perfume, were provoked single-blindly in a placebo-controlled, randomized study. During airway exposure, the eyes were covered and, during the eye exposure, the patients inhaled fresh air. A special face mask or a nose clip was used to avoid any smell. RESULTS: During the 30-min exposure to perfume, there was a gradual increase in three main symptoms; i.e., eye irritation, cough, and dyspnea, after both the airway and eye exposures. The increases were significant compared with placebo. CONCLUSIONS: Asthma-like and other symptoms, such as irritation of the eyes, may be induced by exposure of both the airways and the eyes in patients with sensory hyperreactivity. This points to the importance of studying the sensory nervous system, not only in the airways, but also in other organs.
Adult↗
Adult asthmatics sensitized to cats and dogs: symptoms, severity, and bronchial hyperresponsiveness in patients with furred animals at home and patients without these animals.
BACKGROUND: Domestic furred animals are important sources of allergens in asthma, but few clinical studies have investigated the effects of exposure to or elimination of these allergens. The objective of this study was to investigate whether pet-sensitized asthmatics with pets at home have worsened asthma, compared with similar asthmatics without pets. METHODS: In a cross-sectional epidemiologic study, 129 adult asthmatics sensitized to cats or dogs were investigated by interviews, skin prick tests, specific IgE, eosinophil counts, and bronchial methacholine challenge tests. Patients with a cat or dog at home (n=39) were compared with subjects without pets (n=90). RESULTS: More subjects with pets had symptoms, inhaled or oral steroids, abnormal peak-flow records, higher eosinophil counts, and a higher degree of bronchial hyperresponsiveness than subjects without pets. Asthmatics with pets more frequently ascribed their symptoms to their home environment, but fewer of them reported that their symptoms were elicited by contact with cats or dogs. CONCLUSIONS: This study strongly indicates that living with a cat or a dog aggravates symptoms and biomarkers of airway inflammation in asthmatics sensitized to cats or dogs. The study indicates that avoidance of these allergens may be an important measure in the treatment of sensitized asthmatics.
Adolescent↗
Effect of topical corticosteroids on seasonal increases in epithelial eosinophils and mast cells in allergic rhinitis: a comparison of nasal brush and biopsy methods.
BACKGROUND: Nasal brushing and nasal biopsy are well-tolerated sampling techniques. Seasonal grass pollen-induced rhinitis is characterized by epithelial mast cell infiltration and seasonal increases in both epithelial and sub-mucosal eosinophils. OBJECTIVE: To compare the ability of the nasal brush and nasal biopsy techniques to detect natural seasonal increases in eosinophils and mast cells, and to assess the influence of topical corticosteroid. METHODS: Nasal brush samples and nasal biopsies were collected from 46 grass pollen-sensitive seasonal rhinitis patients before the grass pollen season and at the peak of the pollen season following 6 weeks' treatment with either fluticasone propionate aqueous nasal spray (200 microg, twice daily) or placebo nasal spray. RESULTS: Placebo patients showed seasonal increases in epithelial eosinophils both with nasal brushing (P < 0.0001) and biopsy (P < 0.001). Epithelial mast cell numbers also increased during the pollen season as detectable by brushing (P < 0.0001) and biopsy (P < 0.03). Changes in cell numbers measured by nasal brushing correlated with those observed with nasal biopsy, both for eosinophils and mast cells (P < 0.05). Sub-mucosal eosinophils but not mast cells also increased during the pollen season (P < 0.002). Nasal brushing and biopsy revealed that fluticasone treatment inhibited seasonal increases in epithelial eosinophils (P < 0.00001) and epithelial infiltration by mast cells (nasal brushing P < 0.00001 and nasal biopsy P < 0.01). Fluticasone also inhibited seasonal increases in sub-mucosal eosinophils (P < 0.001) and significantly reduced nasal symptoms (P < 0.001). CONCLUSION: Nasal brushing harvests sufficient inflammatory cells from the surface of the nasal mucosa to be used in lieu of nasal biopsies in observation of the effect of drugs on the nasal epithelium.
Administration, Topical↗
The risk of asthma in relation to occupational exposures: a case-control study from a Swedish city.
The purpose of this study was to estimate the risk of adult asthma in relation to certain occupational exposures. The study was designed as a case-control study in Göteborg, including 321 subjects with asthma, born between 1926 and 1970. Controls (n=1,459) were randomly selected from the same area from registers of the 1986 population. Questionnaire information was collected in 1996, and included occupational exposures and smoking habits. Odds ratios were calculated for exposure before asthma onset, stratified by sex and age-class. The highest risks for asthma were associated with exposure to grain dust (odds ratio (OR) 4.2, 95% confidence interval (CI) 1.6-10.7) and flour dust (OR 2.8, 95% CI 1.1-7.2). Among males, significantly increased risks were observed after exposure to flour dust, welding fumes, man-made mineral fibres, and solvents. Among females, increased risks for asthma were associated with exposures to paper dust and textile dust. In logistic regression models controlling for age, smoking, sex and interacting exposures, increased risks were seen for welding fumes (OR 2.0, 95% CI 15-3.4), man-made mineral fibres (OR 2.6, 95% CI 1.4-7.3) and solvents (OR 2.2, 95% CI 1.2-3.2). The fraction of asthma attributed to occupational exposures after adjusting for sex, smoking and age was 11% (95% CI 7-14%). In conclusion, exposure to welding fumes, man-made mineral fibres, solvents and textile dust is associated with increased risk for asthma.
Adult↗