Presence Of Bronchial Hyperreactivity Research Articles

Bronchial reactivity to inhaled hypertonic saline solutions in children with cystic fibrosis

Background. Inhaled hypertonic saline solutions (IHSS) are included in the list of mandatory prescriptions in the treatment of cystic fibrosis (CF). However, some patients with CF may develop bronchial hyperreactivity (BHR), which may be the cause of violation of the treatment protocol. The purpose is to study the state of bronchial reactivity to IHSS and its dependence on the clinical, functional and microbiological features of CF course in children. Materials and methods. Forty children with CF were examined. All of them underwent general clinical, molecular genetic, laboratory and microbiological examination. Instrumental methods included spirometry, measurement of fractional exhaled nitric oxide, X-ray and computer tomography of the chest. To determine the individual tolerance of inhalations of hypertonic sodium chloride solution (HSCS), the research protocol proposed by E.P. Dellon et al. was used. Results. According to the results of the research protocol, 17 (42.5 %) patients with CF had BHR to HSCS. The highest frequency of BHR was found in children with a severe CF course. There was no dependence of BHR in CF patients on allergic pathology and a burdened allergic history. Assessment of the tolerance of HSCS before prescribing basic therapy is important. Early functional signs of BHR, which may require the preventive administration of short-acting β2-agonists when using HSCS in children with CF, are as follows: reduction in forced expiratory volume in 1 second by 7 % and maximal expiratory flow at 25 % by 6 % when using 3% HSCS. Conclusions. The presence of BHR in patients with CF may interfere with adequate basic therapy by inhalation. The prescription of IHSS to patients with CF should be personalized with the determination of individual sensitivity of a person to predict a positive therapeutic effect.

CATALASE CRS-262T GENE POLYMORPHISM AND CHANGES IN VENTILATION LUNG CAPACITY IN CHILDREN-RESIDENTS OF RADIOACTIVELY CONTAMINATED TERRITORIES.

to determine the association of catalase С-262Т gene polymorphism with the presence of bronchial hyper-reactivity in children living in radioactively contaminated territories. There were examined school-age children-residents of radioactively contaminated territories (RCT), who did not have clinical signs of respiratory pathology. Catalase (CAT) С-262Т gene deletion polymorphism was studied in the molecular genetic laboratory of the State Institution «Reference Center for Molecular Diagnostic of Public Health Ministry of Ukraine». Determination of the polymorphic variant by the catalase С-262Т gene was performed by Polymerase Chain Reaction (PCR) using specific oligonucleotide primers, followed by Restriction Fragment Length Polymorphism (RFLP) analysis. The CAT С-262Т gene polymorphism in children living in RCT was compared with that in the reference group of practically healthy individuals. Ventilation lung capacity was performed by computer spirometry according to the analysis of the loop «the flow-volume». A pharmacological inhalation test with a bronchodilator that acts on β2-adrenergic receptors of the lungs was used to detect early changes in the ventilatory capacity of the lungs - bronchial hyperreactivity. Comparative analysis showed that in the presence of bronchial hyperreactivity in children living in RCT, the CT genotype was more common than in children without bronchial hyperreactivity, and the frequency of the CC genotype was correspondingly reduced. There was a trend towards a decrease in the frequency of the TT genotype. An analysis of the frequency distribution of allelic variants of the CAT С-262Т gene polymorphism in children living in the RCT revealed a tendency to increase in the frequency of the T-allele and according to the decrease in the frequency of C-allele in the presence of bronchial hyperreactivity.Сonclusions. Thus, among children living in RCT, CT-homozygotes of CAT С-262Т gene polymorphism had bronchial hyperreactivity probably more often than CC-heterozygotes. In the presence of bronchial hyperreactivity, there was a trend towards an increase in the frequency of the T-allele and, accordingly, a decrease in the frequency of the C-allele.

Bronchial thermoplasty and the role of airway smooth muscle: are we on the right direction?

Asthma is characterized by inflammation of the airways that includes eosinophils, basal membrane thickening, epithelial sloughing, vascular changes, smooth muscle hypertrophy and hyperplasia, and mucous gland hyperplasia. Recently, there have been studies on the role of hypersensitivity and inflammation in asthma, but the role of bronchial smooth muscle remains unclear. Bronchial thermoplasty is an endoscopic procedure that is approved by the US Food and Drug Administration (FDA) for the treatment of severe refractory asthma, based on the local delivery of radio frequency at 65°C to the airways, with the aim of controlling bronchospasm through a reduction of airway smooth muscle (ASM). Several recent studies have shown significant improvement in clinical outcomes of bronchial thermoplasty for asthma, including symptom control, reduction in exacerbation and hospitalization rates, improved quality of life, and reduction in number of working days or school days lost due to asthma. Data from these recent studies have shown reduction in ASM following bronchial thermoplasty and changes in inflammation patterns. It has also been argued that bronchial thermoplasty may have modulating effects on neuroendocrine epithelial cells, bronchial nerve endings, TRPV1 nerve receptors, and type-C unmyelinated fibers in the bronchial mucosa. This may involve interrupting the central and local reflexes responsible for the activation of bronchospasm in the presence of bronchial hyperreactivity. Several questions remain regarding the use of bronchial thermoplasty, mechanism of action, selection of appropriate patients, and long-term effects. In this review, the role of ASM in the pathogenesis of asthma and the key aspects of bronchial thermoplasty are discussed, with a focus on the potential clinical effects of this promising procedure, beyond the reduction in ASM.

Joint incidence of asthma and rhinitis in macedonia.

The concept of “united airways disease”, based on many similar features and mutual interactions in the pathogenesis of asthma (A) and rhinitis (R), has led to an integral approach to their management. We conducted this study to determine the quantity of the problem of joint incidence of A and R in R. Macedonia, and, perhaps to obtain information on a potential causative effect of the two diseases.Three hundred eighty six patients, who presented with wheezing and/or upper respiratory symptoms at the Pulmology and Allergy Clinic, Skopje, were included during a period of 48 months. The presence of bronchial hyperreactivity – BHR (positive histamine challenge), atopy (prick test to seasonal or perennial inhaled allergens), rhinitis symptoms (such as nasal secretion and obstruction) and X-ray of paranasal sinuses was registered by a specially designed questionnaire. R was diagnosed in 106 of the subjects (27.5%), and A in 280 (72.5%). Among the patients with A, co-incidence with R was found in 219 (76.5%). Including X-ray of paranasal sinuses to the diagnostic protocol increased this percentage to over 90% (256 patients). From the 219 patients with A and R together, 127 (57.99%) had positive atopy. On the other hand, 19 (18.0%) of the rhinitis-only patients had positive BHR without asthma symptoms. The follow up of the rhinitis patients with positive BHR revealed 4 patiets who developed asthma within 36 months, but this was also the case with 2 of the subjects with R and negative BHR. In conclusion, the co-incidence of A and R in our material is 78.21%, or 91.4% (including sinusitis); a greater co-existence of A and R is found in atopic patients. The patients with allergic R are at high risk for developing A and should be monitored in the future and the R symptoms should be adequately treated in order to minimize the risk for developing asthma.

Risk factors for persistence of asthma in children: 10-year follow-up

Objective: Risk factors related to the outcome of childhood asthma are not yet well established. We aimed to investigate the long-term outcome for children with asthma to determine the risk factors in predicting persistence of disease. Methods: Sixty-two children with asthma were evaluated retrospectively at the end of a 10-year follow-up. Patients were asked to complete a questionnaire requesting clinical information, and underwent physical examination, skin prick testing, a pulmonary function test and bronchial provocation testing. Immunologic parameters evaluated were allergen-specific IgE and IgG4 levels, and allergen-induced generation of CD4+CD25+ cells. Results: Mean age at final assessment was 15.9 ± 3.6 years, and duration of follow-up was 10.30 ± 1.27 years. Fifty percent of patients outgrew their asthma during the 10-year follow-up period. All the non-atopic patients outgrew their disease during the study period, whereas 67% of atopic patients did not. We identified two risk factors independently related to the persistence of symptoms: presence of bronchial hyper-responsiveness and presence of rhinitis. Atopic children who were in remission demonstrated significantly higher allergen-induced CD4+CD25+ T cells compared to healthy controls. Conclusions: Atopy, presence of rhinitis, positive and presence of bronchial hyper-reactivity are important risk factors for the persistence of asthma in children. Allergen-induced CD4+CD25+ T cells were higher in the atopic children who outgrew their disease, implicating an immunological mechanism of asthma remission in children.

Evaluation of Vascular Endothelial Growth Factor A and Endostatin Levels in Induced Sputum and Relationship to Bronchial Hyperreactivity in Patients with Seasonal Allergic Rhinitis

Studies about the pathogenesis of bronchial hyperreactivity (BHR) in patients with allergic rhinitis (AR) and its relationship with lower airway remodeling are extremely limited. In this study, bronchial vascular remodeling and its relationship with BHR were evaluated by measurement of vascular endothelial growth factor A (VEGF-A) and endostatin in patients with seasonal AR (SAR). The study group consisted of 30 patients with SAR (positive skin test to grass pollens) and 14 healthy controls. Induced sputum and bronchial provocation test (BPT) to methacholine (M) were performed in season. VEGF-A and endostatin levels were measured by ELISA in induced sputum supernatant. The percentages of eosinophils in induced sputum were significantly increased in BHR+ patients (n = 10) with SAR compared with BHR(-) patients (n = 20) with SAR (p < 0.001). There was no correlation between eosinophils and provocative concentration of M required to produce a 20% decrease in forced expiratory volume in 1 second. The levels of VEGF-A were significantly higher in SAR patients with BHR than in SAR patients without BHR and healthy controls (respectively, p = 0.014 and p = 0.04). The levels of endostatin were significantly lower in SAR patients with BHR than in SAR patients without BHR and healthy controls (respectively, p = 0.020 and p = 0.014). The ratio of VEGF-A/endostatin was significantly higher in SAR patients with BHR than in SAR patients without BHR and healthy controls (respectively, p = 0.009 and p = 0.019). In this first study comparing the VEGF-A and endostatin levels of patients with SAR in sputum supernatant, the presence of BHR was shown to be associated with the vascular component of remodeling "angiogenesis."

FEF25–75 Might Be a Predictive Factor for Bronchial Inflammation and Bronchial Hyperreactivity in Adolescents with Allergic Rhinitis

Allergic rhinitis and asthma are closely associated. Bronchial hyperreactivity (BHR) is a pathophysiological characteristic of asthma. Allergic inflammation is characterized by eosinophilic infiltrate and may by indirectly assessed by exhaled nitric oxide (FeNO). Forced expiratory flow between 25 percent and 75 percent of vital capacity (FEF25-75) may predict BHR in adult patients with allergic rhinitis. The aim of this study was to evaluate the presence of BHR in a large group of adolescents with allergic rhinitis and whether FEF25-75 might be related with BHR and FeNO. Methods 150 adolescents with allergic rhinitis were enrolled. Clinical examination, skin prick test, spirometry, methacholine challenge, and FeNO were performed in all patients. Results Severe BHR is quite frequent in allergic adolescents. Impaired FEF25-75 values (such as less than 65 percent of predicted) constitute a relevant predictive factor for severe BHR (OR 4.4). FeNO levels were significantly related with BHR. Conclusion This study provides evidence that impaired FEF25-75 values might predict severe BHR and BHR is related with FeNO in adolescents. Therefore, BHR should be suspected in adolescents with low FEF25-75 values.

Forced expiratory flow between 25 and 75% of vital capacity might be a predictive factor for bronchial hyperreactivity in children with allergic rhinitis, asthma, or both

Allergic rhinitis and asthma are closely associated. Bronchial hyperreactivity (BHR) is a pathophysiological characteristic of asthma. Forced expiratory flow between 25 and 75% of vital capacity (FEF(25-75)) has been previously shown to be able to predict BHR in adult patients with allergic rhinitis. Therefore, the aim of this study was (i) to evaluate the presence of BHR in a large group of children with allergic rhinitis, asthma or both and (ii) to confirm whether FEF(25-75) might be related to BHR and may predict BHR also in a pediatric population. Nine hundred fifty children with allergic rhinitis (350), asthma (300), or both (300) were enrolled. Clinical examination, skin-prick test, spirometry, and methacholine challenge were performed in all patients. Severe BHR was quite frequent in allergic children, mainly in asthmatic patients. FEF(25-75) values were significantly related to BHR grade, mainly in children with rhinitis (r = 0.69). Impaired FEF(25-75) values (such as ≤65% of predicted) constituted a relevant predictive factor for severe BHR, mainly in children with rhinitis (odds ratio, 8.9). In conclusion, this pediatric study confirmed that impaired FEF(25-75) values might predict severe BHR in children, mainly in those with allergic rhinitis. Therefore, low FEF(25-75) values could suggest BHR in children.

RESPONSE TO BRONCHODILATORS AFTER EXERCISE CHALLENGE PREDICTS BRONCHIAL HYPERREACTIVITY

Background. Some subjects with suspected asthma and a negative exercise challenge test (ECT) demonstrate improved expiratory flow rates after administration of bronchodilators (BD) at the end of the ECT (unpublished observation). This study investigated whether this response predicts the presence of bronchial hyperreactivity (BHR). Patients and methods. The study population included 133 young adults (29.4% women) 21.1 ± 4.2 years of age who underwent ECT and a methacholine challenge test (MCT). A receiver-operator-characteristic curve was used to calculate the optimal cutoff level of the response to BD as a predictor of BHR according to MCT. Results. Using a MCT cutoff level of PC20 ≤ 4 mg/mL showed BHR in 12.8% of subjects. Failure to improve FEV1 by 8% after BD administration predicted the absence of BHR with sensitivity, specificity, and positive and negative predictive values of 76.5%, 68.4%, 25.3%, and 95.5%, respectively. Avoiding MCT in subjects with less than 8% response to BD would have saved 62....

Anästhesie bei Lungenerkrankungen - Postoperative pulmonale Komplikationen: Pathophysiologie und Prophylaxe

Postoperative pulmonary complications (PPC) are considered a main factor increasing postoperative morbidity and mortality. Medical history and clinical examination are highly predictive for the development of PPC. Extended evaluation is indicated in the presence of pulmonary symptoms. Prophylaxis of PPC includes cessation of smoking, antiinfectious measures, optimization of bronchodilator therapy and improvement of cardiac performance. Regional anesthesia is favorable in the presence of bronchial hyperreactivity and for postoperative pain therapy. Postoperative course includes early extubation besides positioning, relief of intrabdominal pressure and physiotherapy.

Response to Bronchodilators After Exercise Challenge Predicts Bronchial Hyperreactivity

Background. Some subjects with suspected asthma and a negative exercise challenge test (ECT) demonstrate improved expiratory flow rates after administration of bronchodilators (BD) at the end of the ECT (unpublished observation). This study investigated whether this response predicts the presence of bronchial hyperreactivity (BHR). Patients and methods. The study population included 133 young adults (29.4% women) 21.1 ± 4.2 years of age who underwent ECT and a methacholine challenge test (MCT). A receiver-operator-characteristic curve was used to calculate the optimal cutoff level of the response to BD as a predictor of BHR according to MCT. Results. Using a MCT cutoff level of PC20 ≤ 4 mg/mL showed BHR in 12.8% of subjects. Failure to improve FEV1 by 8% after BD administration predicted the absence of BHR with sensitivity, specificity, and positive and negative predictive values of 76.5%, 68.4%, 25.3%, and 95.5%, respectively. Avoiding MCT in subjects with less than 8% response to BD would have saved 62.5% of the MCTs and would have missed only four (3%) patients with BHR. Conclusions. BD should be administered routinely after ECT, as the response may be used as a simple, inexpensive tool to predict BHR in young patients and may substantially reduce the number of unnecessary MCTs

Occupational asthma: an assessment of diagnostic agreement between physicians

Objectives: To investigate the levels of agreement between expert respiratory physicians when making a diagnosis of occupational asthma. Methods: 19 cases of possible occupational asthma were identified as part of...

Development of Bronchoconstriction After Administration of Muscle Relaxants in Rabbits with Normal or Hyperreactive Airways

Neuromuscular blocking drugs can induce intraoperative bronchospasm. We characterized the magnitude and the temporal profile of the constriction in normal or in hyperresponsive airways after injections of neuromuscular blocking drugs. Respiratory system impedance (Zrs) was measured continuously over a 90-s apneic period in naïve and rabbits sensitized to allergens by ovalbumin. Fifteen s after the start of Zrs recordings, succinylcholine, mivacurium, or pipecuronium was administered in random order. Zrs was then also recorded during the administration of increasing doses of exogenous histamine. To monitor the changes in the airway mechanics during these maneuvers, Zrs was averaged for 2-s time windows, and the airway resistance (Raw) was determined by model fitting. The increases in Raw were significantly larger in the sensitized rabbits than in the naïve animals. The largest increases in Raw and the maximum rate of change in Raw were obtained for succinylcholine (146% +/- 29% and 0.80 +/- 0.12 cm H2O/L, respectively) and mivacurium (80% +/- 25% and 0.71 +/- 0.13 cm H2O/L) and the smallest were obtained for pipecuronium (40% +/- 12% and 0.41 +/- 0.04 cm H2O/L). Allergic sensitization leads to severe and rapidly developing bronchospasm after administrations of mivacurium or succinylcholine. These deleterious side effects should be considered when succinylcholine or mivacurium is administered in the presence of bronchial hyperreactivity.

Introducción

Asthma is the most frequent chronic disease in childhood. Its prevalence varies (in Spain between 12 % in coastal regions and 6 % in the Castilian plateau). Asthma represents chronic inflammation of the airways associated with an increase in bronchial reactivity to various stimuli, leading to reduced air flow and subsequent remodeling of the bronchial wall. Asthma usually begins in the first few years of life and 30 % of patients will continue to be asthmatic throughout their lives. The main characteristic associated with the persistence of asthma in adulthood seems to be allergy. Another risk factor is the presence of bronchial hyperreactivity. Wheezing associated with viral infections in childhood shows a favorable outcome when not associated with atopic features. The atopic disposition is caused by the interaction between genetic and distinct environmental factors (allergens), as well as by the various clinical manifestations that favor a mainly Th2 response, with interleukins that lead to the formation of specific IgE, pro-inflammatory cytokines, bronchial hyperreactivity, etc. In most cases, asthma is mainly an allergic process, mediated by an IgE mechanism. Inhalation of allergens is considered the most important cause of the onset of asthma in predisposed children. First the presence of an allergen gives rise to sensitization, with the formation of specific IgE. In a subsequent contact, mediators are released, with inflammatory response of the airways and an increase in bronchial hyperreactivity. If the presence of the allergen is prolonged, inflammation and subsequent healing may lead to irreversible damage to the bronchial wall and permanent deterioration of respiratory function. In children with asthma, the aim is to modify the natural history of the disease and prevent its persistence in adulthood. This involves identifying the allergen or allergens causing the symptoms, confirming the role of these allergens in clinical manifestations through specific challenge tests and, lastly, indicating the treatment be followed.

BRONCHIAL ASTHMA AND HYPERREACTIVITY AFTER EARLY CHILDHOOD BRONCHIOLITIS OR PNEUMONIA

The risk of asthma after infantile bronchiolitis is definitely increased over the risk in the general population. A long-term follow-up of bronchiolitis patients found 15% go on to have asthma. Furthermore, the presence of bronchial hyperreactivity in these patients is four times as frequent as overt clinical asthma. Infants with pneumonia are also at increased risk for bronchial hyper-reactivity at a later time but not as likely to develop clinical asthma.

Asthma and Asthma-like Symptoms in Adults Assessed by Questionnaires: A Literature Review

The first widely used questionnaire in respiratory epidemiology was the questionnaire from the Medical Research Council (MRC) of Great Britain. In the first version, from 1960, there were only a few questions about wheezing, but in later editions, more questions about asthma and asthma-like symptoms were added. The MRC questionnaire initiated the development of other questionnaires such as the European Community for Coal and Steel (ECSC) questionnaire of respiratory symptoms and the questionnaire from the American Thoracic Society and the Division of Lung Diseases (ATS-DLD-78). In Tucson, Ariz, a questionnaire was developed in the 1970s that was focused on the subject's own report of asthma. In Great Britain, a questionnaire was developed in the 1980s with the intention of finding the most valid symptom-based items for identifying asthma, "the IUATLD (1984) questionnaire." When judging the validity of a questionnaire, it is essential to understand sensitivity and specificity. Sensitivity is the fraction of the truly diseased subjects found to be diseased using the questionnaire. Specificity is the fraction of the truly healthy subjects found to be healthy using the questionnaire. Regarding questionnaires dealing with asthma, the situation is confusing because of the absence of any gold standard for asthma. The most usual mode of validation has been to test the questionnaire against the results of a clinical physiologic investigation, often a nonspecific bronchial challenge test. Another approach has been to compare the answers from the questionnaire with the clinical diagnoses of asthma. When validated in relation to bronchial challenge tests, the questions about self-reported asthma have a mean sensitivity of 36 percent (range, 7 to 80 percent) and a mean specificity of 94 percent (range, 74 to 100 percent). The questions about "physician-diagnosed asthma" have even higher specificity, 99 percent. When validated in relation to a clinical diagnosis of asthma, the mean sensitivity for the question about self-reported asthma was 68 percent in the reviewed studies (range, 48 to 100 percent). The specificity was 94 percent (range, 78 to 100 percent). One problem in using the presence of bronchial hyperreactivity (BHR) as a gold standard for asthma is that many people with BHR report no respiratory complaints. In other words, the presence of BHR is a measure with high sensitivity but low specificity for asthma. The effect of using a methacholine challenge test as a standard for the disease will thus be an underestimation of the sensitivity of the questionnaire.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of factors associated with bronchial hyperreactivity to methacholine in bronchiectasis

Nonspecific bronchial hyperreactivity (BHR) has been reported to occur in patients with bronchiectasis. To evaluate this further, we studied 77 patients with stable bronchiectasis (noncystic fibrosis) with special reference to the prevalence of BHR to methacholine (MCh), and its relation to lung function, sputum characteristics, concommitant asthma, and atopy. The concentration of MCh required to produce a fall of 20% in forced expiratory volume in 1 s (FEV1), PC20, was determined by Wright's nebulization tidal breathing method. BHR defined by a PC20 greater than or equal to 8 mg/ml was found in 21 of 47 (45%) subjects who underwent bronchial challenge. Presence of BHR was positively associated with low baseline spirometric values, diagnosis of asthma, long duration of disease, and elevated total IgE on univariant analysis, and was significantly related to FEV1/forced vital capacity (FVC) ratio and asthma on multiple regression analysis. Ten of the 21 hyperreactive subjects did not have clinical asthma, whereas all 11 of 22 subjects with clinical asthma who underwent bronchial challenge were hyperreactive. Among those with BHR, there was a positive correlation between PC20 and baseline FEV1. When patients were further classified into asthmatic and nonasthmatic subjects, a positive correlation between PC20 and FEV1 was seen only in those without asthma. Frequency of infective episodes and inflammatory score of sputum assessed by average daily volume, purulence, and leukocyte count did not differ significantly in the groups with and without BHR. These results suggest that BHR in patients with bronchiectasis is associated with coexistent asthma and worse spriometric values, and not with the severity of bronchial sepsis.

Absence and Labour Turnover in a Foundry Attributable to Respiratory Disease

A survey of foundry workers was undertaken to assess the effect of respiratory disease on both absence in the year prior to the survey and labour turnover since a cross-sectional study of respiratory morbidity five years previously. The presence of a wheeze, but not an objective disturbance of airway function, was predictive of absence. Those with respiratory illness, detected in the survey five years previously, were no more likely to have left the foundry than those without such illness. Limited job opportunities may discourage moulders with respiratory disease from leaving the foundry. Absence was not related to cigarette smoking, the presence of bronchial hyperreactivity, or a positive skin test to common allergens. In view of the small number of subjects in this study, studies of larger work populations should be undertaken to further assess the effect of subjective and objective indices of respiratory morbidity on absence and labour turnover.

Respiratory abnormalities among workers in an iron and steel foundry.

A study of the health of 78 workers in an iron and steel foundry in Vancouver, British Columbia, was carried out and the results compared with those found in 372 railway repair yard workers who were not significantly exposed to air contaminants at work. The foundry workers were exposed to PepSet, which consists of diphenyl methane diisocyanate (MDI) and phenol formaldehyde and their decomposition products as well as to silica containing particulates. A questionnaire was administered by trained interviewers, and chest radiography, allergy skin tests, pulmonary function tests, and methacholine inhalation tests were carried out as well as measurement levels of dust and MDI. Compared with the controls, the foundry workers had more respiratory symptoms and a significantly lower mean FEV1 and FEF25-75% after adjustments had been made for differences in age, height, and smoking habit. Three workers (4.8%) had radiographic evidence of pneumoconiosis and 12 (18.2%) had asthma defined as presence of bronchial hyperreactivity, cough, and additional respiratory symptoms such as wheeze, chest tightness, or breathlessness. Sensitisation to MDI is probably the cause of asthma in these workers.