Airway hyperresponsiveness to inhalational challenge with methacholine (MCh) develops by 32 h after allergen challenge of actively sensitized BN rats. To test the hypothesis that CD4+ T cells mediate allergen-induced hyperresponsiveness independent of IgE-mediated mechanisms, we administered CD4+ T cells, CD8+ T cells, and a mixture of CD4+ and CD8+ T cells (total T cells) isolated from the cervical lymph nodes of rats sensitized with ovalbumin (OA) to naive BN rats that underwent aerosol challenge with either OA or bovine serum albumin (BSA) 2 d later. Responsiveness to MCh was measured 2 d before transfer of T cells and 32 h after challenge with OA or BSA. Airway responsiveness increased significantly in recipients of CD4+ T cells after OA challenge, but not in any other of the treatment groups. Analysis of bronchoalveolar lavage (BAL) cells for major basic protein expression by immunostaining showed eosinophilia in OA-challenged CD4+ and total T-cell recipients. Cells retrieved by bronchoalveolar lavage showed increased expression of IL-5 mRNA (in situ hybridization) in CD4+ T cell recipients after OA challenge compared with other groups. Interferon-gamma mRNA was expressed to the greatest extent in CD8+ recipients, but it was elevated in both OA- and BSA-challenged animals. We conclude that CD4+ T cells can induce airway hyperresponsiveness after inhalational challenge with allergen and this is associated with IL-5 production and eosinophilia. CD8+ T cells may have a negative regulatory effect on responsiveness, possibly mediated by interferon-gamma.
Cold air inhalation and exercise-induced bronchoconstriction in relationship to metacholine bronchial responsiveness: different patterns in asthmatic children and children with other chronic lung diseases.
Cold air inhalation and exercise-induced bronchoconstriction (EIB) have both been used as measures of bronchial responsiveness. Both stimuli are often combined in the Nordic climate. The main objective of the present study was to investigate the climatic influence of cold temperatures upon exercise-induced asthma. The secondary aims were: (a) to assess metacholine bronchial hyper-responsiveness and EIB in children with bronchial asthma (n = 32; mean age 10.8 years) compared to children with other chronic lung diseases (CLD) (n = 26, mean age 10.1 years); and (b) to assess the influence of cold air inhalation upon EIB in the two groups of children. Methods used were: (a) the metacholine concentration causing a reduction in FEV1 of 20% (PC20-M), (b) maximum FEV1 fall (delta FEV1) after submaximal treadmill run (EIB test); and (c) delta FEV1 after submaximal treadmill run while inhaling cold (-20 degrees C) dry air (CA-EIB test). Geometric mean PC20-M did not differ significantly between the asthma children (1.28 mg ml-1) and the CLD children (2.90 mg ml-1). In the asthma children, mean delta FEV1 after EIB test was 12.8% vs 21.8% after adding cold air (P
To determine whether measurement of airways responsiveness to methacholine can help physicians diagnose asthma in children.
Children from the 1995 Manitoba birth cohort were assessed by asthma specialists, had skin testing and measurement of airways responsiveness to methacholine (PC20). We selected children with doctor-diagnosed asthma and healthy children as controls (no asthma, no allergic rhinitis, negative skin tests). Sensitivities and specificities for asthma were calculated. Receiver operating curves were calculated to determine the best fit of the methacholine challenge as a diagnostic test.
640 children were assessed. Two hundred fifteen children with doctor diagnosed asthma and 197 healthy controls successfully completed a methacholine challenge. Airways hyperresponsiveness was a moderately sensitive and specific measure for the diagnosis of asthma in girls, whether atopic (sensitivity of 71% and specificity of 69% at PC20
Exhaled nitric oxide is a potential marker of lower airway inflammation. Allergic rhinitis is associated with asthma and bronchial hyperresponsiveness. To determine whether or not nasal and exhaled NO concentrations are increased in allergic rhinitis and to assess the relation between hyperresponsiveness and exhaled NO, 46 rhinitic and 12 control subjects, all nonasthmatic nonsmokers without upper respiratory tract infection, were randomly selected from a large-scale epidemiological survey in Central Norway. All were investigated with flow-volume spirometry, methacholine provocation test, allergy testing and measurement of nasal and exhaled NO concentration in the nonpollen season. Eighteen rhinitic subjects completed an identical follow-up investigation during the following pollen season. Exhaled NO was significantly elevated in allergic rhinitis in the nonpollen season, especially in perennially sensitized subjects, as compared with controls (p=0.01), and increased further in the pollen season (p=0.04), mainly due to a two-fold increase in those with seasonal sensitization. Nasal NO was not significantly different from controls in the nonpollen season and did not increase significantly in the pollen season. Exhaled NO was increased in hyperresponsive subjects, and decreased significantly after methacholine-induced bronchoconstriction, suggesting that NO production occurs in the peripheral airways. In allergic rhinitis, an increase in exhaled nitric oxide on allergen exposure, particularly in hyperresponsive subjects, may be suggestive of airway inflammation and an increased risk for developing asthma.
The aim of the study was to investigate the prevalence of asthma with or without exercise induced symptoms among elite and elite aspiring swimmers and to compare sport specific exercise provocation with mannitol provocation.
101 adolescent swimmers were investigated with mannitol provocation and sport specific exercise challenge test. Mannitol positivity was defined as either direct FEV(1) PD15 (ordinary criteria) or as ß(2)-reversibility =15% after challenge (extended criteria). A direct positive exercise test was defined as a drop in FEV(1) of 10% (ordinary criteria) or a difference in FEV of =15% either spontaneous, variability, or with ß2-agonist, reversibility (extended criteria).
We found a high prevalence of mannitol and/or exercise positivity. Twenty-six swimmers were mannitol direct positive and 14 were direct exercise positive using ordinary criteria. Using extended criteria 43 were mannitol positive and 24 were exercise positive. When including reversibility and variability to define a positive test the sensitivity for current asthma with or without exercise induced symptoms increased while the specificity remained roughly unchanged. Direct positivity for mannitol and exercise poorly overlapped using ordinary criteria but improved using extended criteria.
We found a high prevalence of asthma among elite swimmers. The use of variability and reversibility (liability) as additional criteria to define a positive test provided to our mind relevant information and should be considered.
The purpose of the present investigation was to study bronchial responsiveness and pulmonary function in Swedish sawmill workers, who are not exposed to plicatic acid, the sensitizer in red wood cedar asthma. Bronchial responsiveness, transfer factor, spirometry, and precipitating antibodies in serum against sawmill fungi were measured in 164 workers at five sawmills. The results from workers inside the sawing area (sawyers, n=59), in the trimming department (trimmers, n=66), and from other workers in the sawmill (sawyer-referents, n=39) were compared. Sawyers had higher bronchial responsiveness than referents. In 55% of the sawyers FEV1 decreased by 20% or more within the highest dose of methacholine compared with 31% of sawyer-referents and 41% of trimmers (p
The aim of this study was to investigate whether asthma is associated with decreased quality of sleep and increased daytime sleepiness. The study involved a random population of 2,202 subjects supplemented by 459 subjects with suspected asthma, aged 20-45 yrs. The subjects were from Reykjavik (Iceland), Uppsala and Göteborg (Sweden) and Antwerp (Belgium), and participated in the European Community Respiratory Health Survey. The investigation included a structured interview, methacholine challenge, skinprick tests and a questionnaire on sleep disturbances. Participants in Iceland and Sweden also estimated their sleep times and made peak expiratory flow (PEF) recordings during a period of 1 week. Asthma was defined as self-reported physician-diagnosed asthma with current asthma-related symptoms (n = 267). Difficulties inducing sleep (DIS) and early morning awakenings (EMA) were about twice as common, and daytime sleepiness 50% more common, in asthmatics compared with subjects without asthma. After adjusting for possible confounders, a positive association was found between asthma and: DIS (odds ratio (OR) = 1.8); EMA (OR = 2.0); daytime sleepiness (OR = 1.6); snoring (OR = 1.7); and self reported apnoeas (OR = 3.7). Allergic rhinitis, which was reported by 71% of subjects with asthma, was independently related to DIS (OR = 2.0) and daytime sleepiness (OR = 1.3). A significant correlation was found between the number of asthma-related symptoms and sleep disturbances (p
BACKGROUND: The definition or diagnosis of asthma is a challenge for both clinicians and epidemiologists. Symptom history is usually supplemented with tests of bronchial hyperresponsiveness (BHR) in spite of their uncertainty in improving diagnostic accuracy. METHODS: To assess the interrelationship between respiratory symptoms, BHR, and clinical diagnosis of asthma, the respiratory symptoms of 1633 schoolchildren were screened using a questionnaire (response rate 81.2%) and a clinical study was conducted in a subsample of 247 children. Data from a free running test and a methacholine inhalation challenge test were available in 218 children. The diagnosis of asthma was confirmed by a paediatric allergist. RESULTS: Despite their high specificity (>0.97), BHR tests did not significantly improve the diagnostic accuracy after the symptom history: area under the receiver operator characteristic (ROC) curve was 0.90 for a logistic regression model with four symptoms and 0.94 for the symptoms with free running test and methacholine inhalation challenge results. On the other hand, BHR tests had low sensitivity (0.35-0.47), whereas several symptoms had both high specificity (>0.97) and sensitivity (>0.7) in relation to clinical asthma, which makes them a better tool for asthma epidemiology than BHR. CONCLUSIONS: Symptom history still forms the basis for defining asthma in both clinical and epidemiological settings. BHR tests only marginally increased the diagnostic accuracy after symptom history had been taken into account. The diagnosis of childhood asthma should not therefore be overlooked in symptomatic cases with no objective evidence of BHR. Moreover, BHR should not be required for defining asthma in epidemiological studies.
To study whether forced expiratory volume in 1 s (FEV1) for the diagnosis of bronchial reactivity by means of the methacholine inhalation challenge test could be appropriately replaced by simple measurements of peak expiratory flow rate (PEFR), 75 consecutively referred asthmatic children aged 6-15 y were examined during a symptom-free period. Their baseline FEV1 and PEFR values ranged from 70 to 130% (mean 99.1) and from 77 to 122% (mean 101.4) of those predicted, respectively. The methacholine inhalation challenge was performed with stepwise doubled cumulative doses and both FEV and PEFR were measured at each step. Of the 67 children who had a 20% reduction in either test, the fall in FEV was achieved after a lower dose of methacholine than the 20% fall in PEFR in 49 cases, after a higher dose in 15 and after the same dose in 3. There was a significant correlation (r = 0.56, p
Data concerning the determinants of sputum eosinophilia and bronchial hyper-responsiveness (BHR) in large cohorts of individuals with normal lung function are limited. Here, we assessed the occurrence of sputum eosinophilia and BHR and identified the risk factors for these variables in two populations living in North Karelia, Finland, and in Pitkäranta, the Republic of Karelia, Russia. These areas are geographically adjacent, but differ, however, fundamentally in major cultural, socioeconomical and lifestyle aspects. The study population comprised 790 Finns and 387 Russian, aged 25-54 years, who were randomly enrolled from the population registers. A methacholine challenge test to measure BHR was successfully performed in 581 (74%) Finns and 307 (79%) Russians with virtually normal lung function (FEV1 > 70% of predicted). Of these, induced sputum samples were obtained from 41% of the Finns and from 67% of the Russians. The proportion of current smokers was 27% among the former and 42% among the latter. Sputum eosinophilia was assessed using a semi-quantitative method, and total concentrations of sputum eosinophilic cationic protein (ECP) and myeloperoxidase (MPO) were measured using an immunoassay. Risk factors for BHR and sputum eosinophilia were identified with a regression analysis. The prevalence of sputum eosinophilia was 22% among the Finns and 19% among the Russians, and the respective figures for BHR were 14% and 13%. The median ECP concentration in sputum was significantly higher among the Russians as compared with the Finns (P