Methacholine vs adenosine on intra and extrathoracic airway hyperresponsiveness in patients with cough variant asthma

Background: Airway hyperresponsiveness (AHR) can be studied by bronchoprovocation test (BPT) using direct (methacholine – MCh) or indirect (adenosine 5′‐monophosphate – AMP) stimuli. These two substances have not been compared in cough variant asthma (CVA). Objective: We designed a randomized, single‐blind, cross‐over study to compare AMP and MCh in the detection of CVA. Additionally, we examined whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during MCh and AMP helped in the evaluation of CVA. Methods: Patients with CVA with previous positive MCh BPT performed challenges with AMP and MCh. The variables were: (i) a provocative dose producing a 20% fall in forced expiratory volume in 1 s (FEV₁) value (PD₂₀MCh); (ii) a provocative dose producing a 25% fall in the maximal mid‐inspiratory flow (FIF₅₀) from baseline (PD₂₅MCh) for MCh; (iii) a provocative concentration producing a 20% fall in FEV₁ value (PC₂₀AMP) and (iv) a provocative concentration producing a 25% fall in the FIF₅₀ from baseline (PC₂₅AMP) for AMP. Results: All 113 patients with CVA responded to PD₂₀MCh and 96% and 69% responded to PC₂₀AMP, if we used PC₂₀ ≤ 200 mg/ml or PC₂₀ ≤ 100 mg/ml, respectively, with an excellent correlation between these two tests (r = 0.87 and 0.76, respectively). Extrathoracic AHR associated with AHR was found in 10% in MCh challenge and in 11% with AMP challenge and no patients had EAHR alone. Conclusion: Adenosine challenges correlate well with MCh in patients with CVA. A minority (c. 10%) of CVA patients have EAHR as measured by these tests, while most had AHR as assessed with each of the challenge agents.     

Changes in airway inflammation following nasal allergic challenge in patients with seasonal rhinitis

BACKGROUND: Seasonal allergic rhinitis could predispose to the development of chronic bronchial inflammation as observed in asthma. However, direct links between nasal inflammation, bronchial inflammation and airway responsiveness in patients with seasonal allergic rhinitis and without asthma are not fully understood. The aim of this study was to analyse the changes induced by allergic nasal challenge outside the pollen season in airway responsiveness and bronchial inflammation of patients with seasonal allergic rhinitis. METHODS: Nine patients were evaluated after either grass pollens or placebo nasal challenge in a randomized cross-over double-blinded trial. Nasal parameters were recorded hourly and airway responsiveness was assessed by methacholine challenge. Cytological examinations and cytokine measurements were performed in nasal lavage and induced sputum. Eosinophil activation was investigated by eosinophil-cationic protein expression and secretion. RESULTS: Airway responsiveness was increased after allergic nasal challenge. Total eosinophils and eosinophils expressing eosinophil-cationic protein were increased in induced sputum after allergic nasal challenge. Both eosinophil number and eosinophil-cationic protein concentration in induced sputum were correlated to methacholine responsiveness. CONCLUSIONS: These results suggest that eosinophils participate to the bronchial inflammation in patients with seasonal allergic rhinitis following allergic nasal challenge outside the pollen season and might explain changes in airway responsiveness.     

The effect of inhaled thiorphan on allergen-induced airway responses in asthmatic subjects

Background Neuropeptides are likely to be implicated in the pathophysiology of allergen-induced airway responses. However, upon release in the airways, neuropeptides are potentially inactivated by neutral endopeptidase (NEP). Objective We hypothesized that NEP-inhibition by inhaled thiorphan (TH) would increase allergen-induced early (EAR) and late (LAR) asthmatic responses, and allergen-induced airway hyperresponsiveness to histamine in asthmatic subjects in vivo. The dose and dosing intervals of TH were derived from previous pharmacokinetic and dose-finding studies. Methods Nine non-smoking, atopic, asthmatic men with dual asthmatic responses to inhaled house-dust mite extract participated in a double-blind, placebo-controlled, cross-over study. During each study period PC₂₀ histamine was measured 24 h before, and 3 and 24 h post-allergen. TH (1.25 mg/mL, 0.5 mL) or placebo (P) were aerosolized pre-allergen, and three times at 2 h intervals post-allergen (total dose of TH: 2.5mg). Forced expiratory volume in one second (FEV₁) was recorded and expressed as percentage fall from baseline. The EAR (0–3 h) and the LAR (3–8 h) were defined as maximum percentage fall from the pre-allergen baseline and as corresponding areas under the time-response curves (AUC). Results As compared with P, TH failed to induce an acute effect on FEV₁ at any of the timepoints (P > 0.08). There was no significant difference between P and TH in the EAR and the LAR: neither in terms of maximum percentage fall from baseline (mean± SEM: EAR: 22.3 ±4.7% (P) and 20.4±4.1% (TH). P=0.75; LAR: 25.2 ± 4.7% (P) and 26.4±5.8% (TH), P= 0.77) nor in terms of AUC (P = 0.16). Correspondingly, the changes in PC₂₀ histamine were not different between the two treatments (F > 0.40). Conclusion We conclude that four adequate doses of the inhaled NEP-inhibitor, thiorphan. failed to potentiate allergen-induced airway responses in asthma. These results suggest that either neuropeptides do not play a predominant role in allergeninduced airway responses, or that allergen challenge induces NEP-dysfunction in humans in vivo.     

Changes in bronchial hyperresponsiveness following high- and low-sulphite wine challenges in wine-sensitive asthmatic patients

BACKGROUND: Previous studies suggest that challenge of most wine-sensitive asthmatic patients may not result in a reduction in forced expiratory volume in 1 s (FEV(1)). OBJECTIVE: The aim of this study was to assess whether changes in bronchial hyperresponsiveness (BHR) occur following wine challenge of asthmatic patients who report sensitivity to wine, and whether such changes could help clarify the role of sulphite additives in wine-induced asthmatic responses. METHODS: Eight self-reporting wine-sensitive asthmatic patients completed double-blind challenges with high- and low-sulphite wines on separate days. FEV(1) and histamine PC(20) were measured before and after consumption of 150 mL of wine. RESULTS: None of the eight subjects demonstrated a clinically significant >or=15%) reduction in FEV(1) following challenge with either high- or low-sulphite wine. In contrast, one patient demonstrated clinically significant increase in BHR following challenge with both high- and low-sulphite wines, and a smaller increase in BHR following placebo challenge. A second patient showed a significant increase, while another showed a significant decrease in BHR following challenge with low-sulphite wine. A fourth patient showed borderline increases in BHR following challenge with both high- and low-sulphite wines. CONCLUSIONS: Although changes in BHR, in the absence of reductions in FEV(1), were observed in some asthmatic patients following wine challenge, these changes were not consistent with a single aetiology. Consequently, this study did not support a major role for the sulphite additives in wine-induced asthmatic responses in the patients studied. The aetiology of wine-induced asthma is likely to be complex and appears to vary among individuals who are sensitive to these drinks.     

Relationship of skin-prick reactivity to aeroallergens and hyperresponsiveness to challenges with methacholine and adenosine monophosphate

BACKGROUND: Clarification of the relationship between atopy and bronchial hyperresponsiveness (BHR), both key features of asthma, is critical to our understanding of the disease. We therefore investigated the putative relationship between skin-prick reactivity to aeroallergens and BHR to direct and indirect stimuli. METHODS: We performed a retrospective analysis of data from 332 patients presenting with a diagnosis of asthma. Patients were characterized by skin prick tests (SPT), spirometry and bronchial challenge with methacholine and adenosine monophosphate (AMP). RESULTS: For patients who had BHR to methacholine but not AMP, the presence of atopy was associated with a lower PD20 (the provocative dose of methacholine producing a fall in FEV1 of 20%), amounting to a geometric mean (95% confidence interval (CI)) of 2.3-fold (1.4-4.0) difference. Furthermore, the number of skin-prick positive (SPP) responses was related to methacholine reactivity: 0-1 SPP, PD20 = 69.9 micro g; 2-4 SPP, PD20 = 47.8 micro g; 5-8 SPP, PD20 = 35.6 micro g. There was a 2.0- fold (1.1-3.6) difference between the groups with a low (0-1 SPP) and high (5-8 SPP) degree of skin-prick reactivity. A similar pattern was seen when data were analyzed including only perennial allergens. Spirometry was unrelated to the degree of skin-prick reactivity. DISCUSSION: These results suggest that skin-prick reactivity to aeroallergens is associated with BHR to methacholine.     

Urinary LTE4 excretion in antigen-provoked asthmatic patients treated with the inhaled LTD4 antagonist, L-648,051

Leukotriene (LT) E4 represents the major LT metabolite in man, and its urinary excretion can be used as an indirect marker of systemic LTC4 and/or LTD4 synthesis and release. In the present study LTE4 excretion was monitored for 24 h in 12 atopic patients with mild asthma undergoing antigen bronchoprovocation as part of a double-blind, placebo-controlled, two-period cross-over study of the aerosol-delivered LTD4 antagonist, L-648,051. Urinary LTE4 excretion was also studied separately in six of the patients after inhaling only diluent. Urine was sampled before, and serially after antigen challenge, at intervals corresponding to the immediate (0-3 h postchallenge) and late (3-6, 6-12, 12-24 h postchallenge) asthmatic reactions. LTE4 was determined by reversed-phase HPLC and radioimmunoassay. Forced expiratory volume in 1 s (FEV1) was recorded serially through 8 h after inhalation of antigen and diluent. Compared to base-line measurements, antigen bronchoprovocation induced significant increases in mean LTE4 excretion rates 0-3 h postchallenge (i.e. during the immediate asthmatic response) after treatment with both placebo (P < 0.01) and L-648,051 (P < 0.05). These mean LTE4 excretion rates in the immediate phase were also significantly higher than the mean rates in the late phase (3-6 h and beyond); the excretion rates of LTE4 at these later time intervals were similar to base-line values. After inhalation of diluent, the LTE4 excretion rates in the intervals 0-3, 3-6, 6-12 and 12-24 h were unchanged from base-line values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Omalizumab decreases nonspecific airway hyperresponsiveness in vitro

BACKGROUND: In asthmatic patients, both symptoms and hyperresponsiveness are related to immunoglobulin E (IgE) concentration in serum. The anti-IgE monoclonal antibody omalizumab improved the control of asthma, but its effect on airway hyperresponsiveness is controversial. Passive sensitization reproduced in vitro a bronchial hyperresponsiveness, an increase in IgE bearing cells, and a mast cell degranulation. This study was designed to examine the effect of omalizumab on passive sensitization-induced hyperresponsiveness, alterations in IgE positive inflammatory cells and mast cell degranulation within the bronchial wall. METHODS: Proximal (3-5 mm diameter) and distal (0.5-1.5 mm diameter) human bronchi dissected out from 10 lung specimens were incubated in normal or asthmatic serum containing various concentrations of omalizumab. Contractile responses to histamine or Dermatophagoides pteronyssinus (D. pter) were recorded using an organ bath system and expressed as percentage of maximal contractile response to acetylcholine (ACh). Immunohistochemistry was performed using monoclonal antibodies directed against IgE or tryptase. Mast cells were classified as fully granulated (type I), partly (type II) or largely degranulated (type III). RESULTS: The specific bronchial hyperresponsiveness to D. pter and the nonspecific bronchial hyperresponsiveness to histamine following passive sensitization were significantly inhibited by omalizumab in both distal and proximal airways. Passive sensitization-induced increase in IgE positive cells was also abolished by omalizumab in a concentration dependent manner. Mast cell degranulation which was inhibited by omalizumab was positively correlated with the contractile response to D. pter. CONCLUSIONS: Omalizumab blocks specific and nonspecific bronchial hyperresponsiveness. Anti-IgE also decreases IgE bearing cell number and mast cell degranulation.     

Peak expiratory flow variation and bronchial hyperresponsiveness in asthmatic children during periods of antigen avoidance and reexposure

Changes of diurnal variation of peak expiratory flow rate (%PEF variation) and their relationship with bronchial hyperresponsiveness (BHR) to methacholine (PC²⁰) were evaluated in 12 children with mild-to-moderate asthma and house-dust mite allergy, during successive periods of stay in a mite-free environment at high altitude (1756 m) and at their home at sea level. The children remained at the high altitude from October until the end of December; then they spent a 3-week period at home and returned to high altitude residence in January. PEF was measured daily, in the morning and in the evening, during the 3 months' stay at high altitude and then for 10 days after the return in January. PC²⁰ was assessed in 8/12 children, once a month from October to December, and at the return in January. Mean absolute PEF values did not change significantly throughout the study. From October to December, patients showed a significant decrease of mean %PEF variation ( P = 0.04), while PC²⁰ showed an increase ( P = 0.05). After the 3 weeks at home, both %PEF variation ( P = 0.03) and PC²⁰ ( P = 0.05) significantly worsened. The correlation between PC²⁰ values and mean %PEF variation in the 2 days before and after each methacholine test was r =−0.63 ( P = 0.001). Our data suggest that there is a beneficial effect of a prolonged stay in a mite-free environment, on both PEF variability and BHR, also in asthmatic children with good pulmonary function. PEF variability and bronchial responsiveness to methacholine were significantly correlated also for small changes of the two variables.     

High-dose inhaled steroids in the management of asthma A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function

Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV₁ FVC, PEF or the histamine PC₂₀. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.     

A Mononuclear Cell-Derived Histamine Releasing Factor in Asthmatic Patients

In an attempt to study the role of lymphokines in asthma, lymphocytes from asthmatic patients were stimulated in vitro with skin test-positive allergen (dust mite) or with non-specific mitogen-phytohaemagglutinin for 4 h, then washed carefully and cultured alone for 16 h. Cell-free supernatants were subsequently collected and applied in the basophil histamine release test in vitro and in bronchial provocation test and skin prick test in vivo. Supernatant of non-stimulated lymphocytes from asthmatic patients released significant amounts of histamine from basophils. Stimulation of lymphocytes with specific allergen or phytohaemagglutinin augmented the supernatant-induced histamine release. Lymphocyte supernatants from the majority of patients also induced bronchoconstriction and elicited skin wheal and flare reaction in vivo.     

Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma

BACKGROUND: Albeit its exact pathogenesis is still ambiguous; aspirin-intolerant asthma is one of several types of asthma for which antileukotriene therapy is useful, because it is widely accepted that bronchial over-production of leukotrienes may be involved in its pathogenesis. Pranlukast (8-[p-(4-phenylbutyloxy) benzol] amino-2-(tetrazol-5-yl)-4-oxo-4H-1-benzopyran hemihydrate), a selective cysteinyl leukotriene receptor antagonist, is now widely used in the treatment of asthma. OBJECTIVE: This study was designed to investigate the protective effect of pranlukast on airway sensitivity to sulpyrine provocation testing, bronchial responsiveness to methacholine provocation testing, and to investigate whether this protective activity is associated with a reduction in aspirin-induced excretion of urinary LTE4 (uLTE4), a marker of the cysteinyl leukotriene (LT) overproduction that participates in the pathogenesis of aspirin-induced asthma. METHODS: We assessed the effects of pretreatment with pranlukast on bronchoconstriction precipitated by inhalation of methacholine and sulpyrine in 16 adult patients with mild or moderate aspirin-intolerant asthma; those who were in stable clinical condition and were hypersensitive to sulpyrine provocation testing were allocated to this study. A double-blind, randomized, crossover design was used. uLTE4 was measured using combined reverse-phase high-performance liquid chromatography (rp-HPLC)/enzyme immunoassay. RESULTS: Pranlukast protected against analgesic-induced bronchoconstriction through mechanisms that were not related to the bronchodilator property, but were related to the improvement both of bronchial hyperresponsiveness and hypersensitivity to analgesic (P < 0.005 and P < 0.0001). Pranlukast showed little effect on excretion of uLTE4. CONCLUSION: These results support the hypothesis that cysteinyl leukotriene is one of the most important components in the pathogenesis of aspirin-intolerant asthma. Pranlukast improves not only hypersensitivity to analgesic, but also bronchial hyperresponsiveness in aspirin-intolerant asthma. It is also possible that pranlukast has another anti-asthmatic effect besides that of a leukotriene receptor antagonist.     

Bronchial hyperresponsiveness and airway inflammation in adolescents with asymptomatic childhood asthma

BACKGROUND: About 70% of childhood asthmatics become free of asthma-related symptoms during adolescence. Little is known about bronchial hyperresponsiveness (BHR) and airway inflammation in young adults with "outgrown" childhood asthma. METHODS: We studied 61 nonsmoking medical students (18 intermittent mild asthmatics, 23 students with outgrown childhood asthma but free of asthma-related symptoms for 10 years (asymptomatic asthmatics) and 20 healthy students). BHR and lung function were measured, and induced sputum samples analyzed for eosinophil count, eosinophilic cationic protein (ECP), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: BHR was still present in most asymptomatic asthmatics, but it was milder compared with healthy students. Only three subjects with previous asthma had no BHR and no signs of airway inflammation. Percentages of eosinophil, and ECP, TNF-alpha and GM-CSF concentrations in induced sputum of mild asthmatics and asymptomatic asthma groups were higher than in the healthy group. In asymptomatic asthmatics group, the duration of asthma, sputum eosinophil percentage, and the level of TNF-alpha in sputum correlated significantly with BHR. CONCLUSIONS: Only a few subjects with longstanding asymptomatic asthma could be considered as cured; most asymptomatic asthmatics continued to exhibit BHR and signs of airway inflammation. The outcome of childhood asthma and BHR was associated with the degree of airway inflammation and the duration of childhood asthma.     

Effects of ketotifen on symptoms and on bronchial mucosa in patients with atopic asthma

Ketotifen is marketed throughout the world as an antiallergy drug, but whether it affects infiltration of inflammatory cells into airway mucosa is not known. We studied the effects of ketotifen on symptoms, pulmonary function, and airway inflammation in 25 patients with atopic asthma. Patients took ketotifen (1 mg twice daily) or a matching placebo for 8 weeks in a double-blind, parallel-group study. Data recorded on diary cards were used for 2 weeks before treatment began, and they were used for the last 2 weeks of treatment to study asthma symptoms, use of β2–agonists, and peak expiratory flow (PEF). Pulmonary function tests, bronchial responsiveness to methacholine, and fiberoptic bronchoscopy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. Specimens were stained immunohistochemically with monoclonal antibodies against stored eosinophil cationic protein (EG1), the secreted form of eosinophil cationic protein (EG2), mast-cell tryptase (AA1), neutrophil elastase (NP57), CD3, CD4, CD8, and CD25. The numbers of positively stained cells in the lamina propria were counted. Compared with the placebo, the ketotifen-treated group exhibited significant improvement of asthma symptoms ( P <0.05) and bronchial responsiveness (P<0.05). This was accompanied by a reduction of EG2+ eosinophils ( P <0.05), CD3+ T cells ( P <0.001), CD4+ T cells (P<0.01), and CD25+ activated T cells ( P <0.01) in the bronchial mucosa. These results suggested that the beneficial effects of ketotifen in bronchial asthma may result from consequent inhibition of activated eosinophils and T-cell recruitment into the airway. Moreover, ketotifen may relieve allergic inflammation in bronchial asthma.     

Increased frequency of bronchial hyperresponsiveness in patients with inflammatory bowel disease

Although bronchopulmonary manifestations are rare in inflammatory bowel diseases (IBD), subclinical abnormalities have been described in up to 50% of cases. The pathophysiology of these abnormalities remains unknown. However, a latent inflammation of the bronchial mucosa secondary to the inflammation of the intestinal mucosa has been suggested. This subclinical inflammation may lead to increased bronchial responsiveness. We studied the bronchial responsiveness in 38 inflammatory bowel disease (IBD) patients, using the methacholine test. Bronchial hyperresponsiveness was defined by a PC₂₀M <16 mg/ml. Twenty-four healthy controls were also studied. There was no significant difference in baseline FEV₁ between IBD patients and controls. However, there was a significantly greater fall in FEV₁ in the IBD patients at the concentrations of methacholine tested. The frequency of bronchial hyperresponsiveness was significantly higher in the IBD population (45%) than in controls (17%; P <0.03). Atopy, defined by skin test, was more common in IBD patients (42%) than in controls (21%). Even when only nonatopic subjects were considered, the frequency of bronchial hyperresponsiveness was significantly higher in IBD patients (41%) than in controls (5%; P <0.02). Thus, subclinical bronchial hyperresponsiveness is common in IBD, and may be considered a further extraintestinal manifestation.     

Epidemiologic evidence of a relationship between airway hyperresponsiveness and exposure to polluted air

BACKGROUND: There has been an increase in allergic diseases as a result of increased air pollution emanating from traffic and various industries. OBJECTIVE: This study evaluated the association between air pollution and airway hyperresponsiveness in a cross-sectional study of a cohort of 670 children, aged 10-13 years. METHODS: We measured spirometry and conducted allergic skin tests and methacholine challenge tests in 670 schoolchildren. The methacholine concentration causing a 20% fall in FEV1 (PC20) was used as the threshold of airway hyperresponsiveness (AHR). Thresholds of 16 mg/dl or less were assumed to indicate AHR. RESULTS: All of the schoolchildren had normal pulmonary function. Of the children, 257 (38.3%) had AHR. There was a significant increase in AHR in schoolchildren living near a chemical factory [45.0% (138/306), 6.50 +/- 0.48] compared to those in rural [31.9% (52/163), 9.84 +/- 0.83] and coastal [33.3% (67/201), 7.17 +/- 0.68] areas. Atopy was significantly more prevalent near the chemical factory vs the coastal and rural areas [35.6% (109/306) vs 27.3% (55/201) and 23.3% (38/163), respectively, P < 0.007]. Schoolchildren with atopy had lower PC20 than those without atopy (5.98 +/- 0.60 vs 8.15 +/- 0.45, P < 0.001). Positive allergy skin tests and living in a polluted area were risk factors in multivariate analyses adjusted for sex, parents' smoking habits, age, body mass index, nose symptoms and lung symptoms (odds ratio for location = 2.4875, confidence interval 1.6542-3.7406, P < 0.000; odds ratio for allergy skin test = 1.5782, confidence interval 1.1130-2.2379, P < 0.0104). CONCLUSION: Our findings demonstrate that more children living in polluted areas have airway hyperresponsiveness than do those living in less polluted areas.     

Comparison of FEV1 and specific airway conductance in assessing airway response to occupational agents

BACKGROUND: There is theoretical evidence that specific airway conductance (SGaw) could be more reliable than forced expiratory volume in 1 s (FEV1) for assessing changes in airway calibre. We investigated the changes in FEV1 and SGaw when assessing bronchial responses to occupational agents. METHODS: SGaw and FEV1 were measured during inhalation challenges with various occupational agents in 174 consecutive subjects investigated for possible occupational asthma. RESULTS: A decline in SGaw of 50% or greater was documented in 77 of 90 subjects (86%) who showed a >/=20% fall in FEV1 and in 11 of 84 subjects (13%) who failed to demonstrate such a fall in FEV1. Among subjects who developed a >/=20% fall in FEV1, those who failed to develop a >/=50% decline in SGaw had a lower baseline SGaw than those who did. Among the group without a >/=20% fall in FEV1, a >/=50% decrease in SGaw was associated with either an 'intermediate' fall in FEV1 (between 15 and 17% from baseline value) (n = 4), a significant postchallenge increase in nonspecific bronchial hyper-responsiveness to histamine (n = 2), or both features (n = 3). CONCLUSIONS: A decline in SGaw of 50% or greater may provide useful complementary evidence of a bronchial response during challenges that produce equivocal results in FEV1.     

Absence of relationship between tuberculin reactivity and asthmatic symptoms, level of FEV1 and bronchial hyperresponsiveness in BCG vaccinated young adults

BACKGROUND: Some recent studies have suggested that bacillus Calmette-Guérin (BCG) vaccination or mycobacterial infection early in life is inversely related to asthma. We wondered if an increase in tuberculin reactivity was inversely related to commonly used indices of asthma in a population of young adults who were BCG vaccinated at age 14. METHODS: Men and women aged 20-44 years, randomly selected from the general population, were tuberculin tested with the epinephrine-Pirquet method with Norwegian-produced synthetic medium tuberculin (n = 588). In addition they were interviewed using eight questions on asthma symptoms and medication. Lung function and bronchial responsiveness were also tested. RESULTS: Altogether 95% of those studied had been BCG vaccinated at age 14 (n = 558). In the 386 subjects with complete examinations, there was no relationship between a positive tuberculin reaction (> or = 4 mm) and asthma symptoms or use of asthma medication. Furthermore we did not observe any relationship between a positive tuberculin reaction and the level of forced expiratory volume (FEV1) or a positive bronchial responsiveness test, assessed as the percent of predicted of FEV1 and PD20 < 2 mg methacholine, respectively. In multiple logistic regression analyses neither respiratory symptoms, level of FEV1, nor bronchial hyperresponsiveness were related to tuberculin reactivity after adjustment for age, gender and smoking habits. CONCLUSIONS: In this young adult population who were BCG vaccinated at the age of 14 no significant relationship existed between tuberculin reactivity and asthmatic symptoms, level of FEV1 or bronchial hyperresponsiveness. Our data does not support the hypothesis that BCG immunization is beneficial in reducing asthmatic symptoms and disease in young adults.     

Inflammatory cells and eicosanoid mediators in subjects with late asthmatic responses and increases in airway responsiveness

To determine the relationship of inflammatory cells and eicosanoid mediators to the pathogenesis of the late asthmatic response (LAR) and increases in nonspecific airway responsiveness, we studied bronchoalveolar lavage (BAL) cells and fluid in 27 subjects 12 hours after inhaled antigen challenge. Methacholine challenge was performed before antigen challenge and 24 hours later (12 hours after BAL). Eight subjects had no LAR (-LAR, less than or equal to 10% fall in FEV1), nine subjects had an equivocal LAR (+/- LAR, 11% 25% fall in FEV1), and 10 subjects had a definite LAR (+LAR, greater than 25% fall in FEV1). Subjects developing +LAR had increased airway responsiveness at baseline compared with that of subjects developing an +/- LAR, but not with subjects having -LAR. If airway responsiveness was markedly increased at baseline, further increases after antigen challenge were often not observed. We found that both percent neutrophils and eosinophils increased in BAL as the severity of the LAR increased, but significant differences between the groups with -LAR and +LAR were only observed when both cell types were considered together. In addition, there was a significant correlation between the combined cell percentages and the severity of the LAR as determined by fall in FEV1. Likewise, increases in airway responsiveness were associated with significant increases in both neutrophil and eosinophil numbers, but only neutrophils correlated with the change in airway responsiveness after antigen challenge. However, despite the significant physiologic and cellular differences that we found between our groups, no significant differences could be found in BAL eicosanoid-mediator concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)