Asymptomatic Airway Hyperresponsiveness Research Articles

Fat mass index and airway hyperresponsiveness in Korean adults

ABSTRACT Objective Airway hyperresponsiveness (AHR) is associated with asthma and obesity, which is defined as a high body mass index. Body mass mainly comprises fat mass (FM) and muscle mass (MM), which are independent of each other. We investigated the effect of changes in FM over time on the development of asymptomatic AHR in adults. Methods This long-term longitudinal study included adults who were underwent health checkups at the Seoul National University Hospital Gangnam Center. The participants underwent two methacholine bronchial provocation tests with a follow-up period (between the first and second tests) of more than 3 years and bioelectrical impedance analysis (BIA) at all visits. FM index (FMI; FM normalized for height) and MM index (MMI; MM normalized for height) were calculated using BIA. Results The study included 328 adult participants (61 women and 267 men). The mean number of BIA measurements was 6.96 and the follow-up duration was 6.69 years. In total, 13 participants showed a positive conversion of AHR. Multivariate analysis indicated that a high rate of change in FMI ([g/m2]/year), not MMI, was significantly associated with the risk of AHR development (P = 0.037) after adjustment for age, sex, smoking status, and FEV1 predicted. Conclusion A rapid gain of FM over time may be a risk factor for developing AHR in adults. Prospective studies are needed to confirm our results and evaluate the role of FM reduction in preventing AHR development in obese adults.

Predictive factors of asymptomatic airway hyperresponsiveness in chronic rhinosinusitis with nasal polyps

Objective:To explore the predictive factors for asymptomatic airway hyperresponsiveness（AAHR） in patients with chronic rhinosinusitis with nasal polyps（CRSwNP）. Methods:A total of 76 CRSwNP patients who were hospitalized in the Department of Otorhinolaryngology of Fenyang Hospital affiliated to Shanxi Medical University from May 2016 to October 2020 were retrospectively analyzed, including 40 patients in AAHR group and 36 patients in non-airway hyperresponsiveness（non-airway hyperresponsiveness, NAHR） group. The clinical symptoms, CT score of paranasal sinuses, eosinophil（EOS） count in peripheral blood and nasal polyp tissue were compared and analyzed. Logistic regression was used to analyze the risk factors of AAHR, and receiver operating characteristics curve was used to judge the predictive value of the parameters. Results:Compared with NAHR group, AAHR group had more symptoms of mouth breathing and postnasal drip, higher total score of CT in ethmoid sinus, sphenoid sinus, olfactory cleft, and more EOS count in peripheral blood and nasal polyp tissue. The differences were statistically significant. There was a positive correlation between EOS count in peripheral blood and in nasal polyp tissue（r=0.324, P<0.01）. Postnasal drip, high posterior ethmoid sinus（PE） score and nasal polyp tissue EOS count were risk factors for AAHR. The predictive value of nasal polyp tissue EOS count was higher than that of PE score（AUC=0.786 and 0.685, respectively）. When the PE score was ≥1.5, the sensitivity was 80.0% and the specificity was 55.6%. When the nasal polyp tissue EOS count was ≥5.67/HPF, the sensitivity was 82.5% and the specificity was 66.7%. Conclusion:The occurrence of AAHR in patients with CRSwNP was related to clinical symptoms, paranasal sinus CT score, peripheral and nasal polyp tissue EOS count. PE score and nasal polyp tissue EOS count can be used to predict AAHR, however nasal polyp tissue EOS has higher predictive value.

A Comparative Study of Symptoms, Nasal Eosinophilia and Pulmonary Function Tests Before and After Short Term Treatment with Corticosteroid Nasal Spray in Patients with Allergic Rhinitis.

Allergic rhinitis has been on the rise because of urbanization and major population shift in addition to changes in the particulate matter in the atmosphere. Intranasal corticosteroid sprays are recommended as first-line prescription treatment in all cases of allergic rhinitis. The propensity of co-existing non-apparent lower airway hyper-responsiveness is also on the rise and must be evaluated. The aim of this study is to compare the symptomatic improvement, changes in nasal eosinophilia and asymptomatic airway hyper responsiveness before and after short term treatment with steroid nasal spray. Fifty patients meeting the inclusion criteria for allergic rhinitis with no symptoms of asthma underwent pulmonary function tests and assessment of symptoms before and after one-month treatment with inhalational steroid nasal spray (Fluticasone Furoate), in the standard adult dosage. Based on TNSS (Total nasal symptom score) and TOSS (Total ocular symptom score), all 50 patients showed significant improvement after treatment. Among 20 patients with > 50 eosinophils per high power field, 80% had 0-10 eosinophils per high power field on nasal smear after treatment. Among 40 patients with mild large airway obstruction, 37 showed significant improvement in FEV1 data. Also FEV1/FVC data showed significant improvement. Significant improvement (FEF25-75 > 50%) was also noticed in small airway disease after treatment among the 5 patients. The study showed that lower airway hyper responsiveness coexists with allergic rhinitis and treating allergic rhinitis with just steroid nasal spray assists in reducing the former, supporting the concept of Unified Airway Disease (UAD).

Nasal interleukin 25 as a novel biomarker for patients with chronic rhinosinusitis with nasal polyps and airway hypersensitiveness: A pilot study

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airway and is tightly linked with airway hyperresponsiveness (AHR) and asthma. However, the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP remain elusive. ObjectiveTo investigate the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP. MethodsIn this study, sinonasal tissues were collected from 42 patients with CRSwNP (asthma, n = 17; asymptomatic AHR, n = 11; non-AHR, n = 14), 11 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 13 controls. The protein and messenger RNA levels of interleukin (IL) 25 and other cytokines in nasal polyp (NP) and control sinonasal tissues were determined by quantitative real-time polymerase chain reaction and multiplex immunoassay, respectively. Multivariate logistic regression and receiver operating characteristic curve analysis were performed to assess the clinical relevance of IL-25. ResultsWe found that the protein and messenger RNA levels of IL-25 were significantly increased in NP tissues compared with the control sinonasal tissues from patients with CRSwNP, patients with CRSsNP, and controls. Multivariate logistic regression revealed that the nasal IL-25 protein level and nasal and blood eosinophil counts were independent risk factors for AHR in patients with CRSwNP. According to receiver operating characteristic curve analysis, nasal tissue IL-25 had a sensitivity of 91.4% and a specificity of 62.8% (area under the curve, 0.845) at the cutoff level of 5 pg/μL for indicating AHR in this CRSwNP cohort. ConclusionOur findings indicated that IL-25 was significantly increased in NP tissues and may be considered as the molecular indicator for AHR in patients with CRSwNP. Trial RegistrationClinicalTrials.gov Identifier: NCT02110654.

Evaluation of airway hyperresponsiveness in chronic rhinosinusitis: values of sinus computed tomography

BackgroundChronic rhinosinusitis (CRS) is tightly linked to airway hyperresponsiveness (AHR) and asthma. However, the practical surrogate parameters for evaluating AHR in patients with CRS remain unclear. ObjectiveTo evaluate the diagnostic values of sinus computed tomography for AHR in patients with CRS. MethodsWe performed a prospective, single-blinded study of 125 consecutive patients with CRS. These patients were subdivided into AHR and non-AHR (NAHR) groups based on histamine provocation test results. The following parameters were compared between 2 groups of CRS patients: Lund-Mackay scores, olfactory cleft (OC) scores, and serum eosinophil counts. ResultsFifty-seven patients (45.4%) presented with AHR. The OC scores, the ratio of OC scores to total scores, and the eosinophil counts in the AHR group were significantly higher than those in the NAHR group (P < .001). Multivariate logistic regression revealed that OC scores and eosinophil counts were independent risk factors for asymptomatic AHR (OC scores P < .001 and eosinophil counts P = .010). The OC score had a higher predictive value for AHR (area under curve, 0.800) than eosinophil counts (area under the curve, 0.637). When the OC score was 3 or higher, the sensitivity was 75.0%, specificity was 77.9%, and positive predictive value was 68.8%. ConclusionThe findings validate a prospective assessment of sinus computed tomography as a screening tool for AHR in patients with CRS.

The CC16 A38G polymorphism is associated with asymptomatic airway hyper-responsiveness and development of late-onset asthma

BackgroundClara cell secretory protein (CC16) is expressed primarily in the respiratory tract and is a potent anti-inflammatory agent that protects the airway from inflammation. The associations of the A38G polymorphism in this gene with asymptomatic airway hyper-responsiveness (AHR), which is considered a risk factor for future asthma in adults, and the development of adult-onset asthma are unclear. ObjectiveTo evaluate the association of the CC16 A38G polymorphism with asymptomatic AHR in healthy young adults and the development of adult-onset asthma and the association between plasma CC16 level according to this genotype and asymptomatic AHR. MethodsNonspecific AHR was measured in 154 asymptomatic, young, healthy adults using a continuous methacholine inhalation method. The cumulative dose values of inhaled methacholine measured at the inflection point at which respiratory conductance started to decrease (Dmin) were used as an index of AHR. Case–control analysis was performed for the association between this polymorphism and the development of asthma in 1,086 unrelated Japanese subjects (504 subjects with asthma and 582 healthy subjects). ResultsThe 38AA + AG genotype was associated with lower Dmin values and lower plasma CC16 levels (P = .012 and .020). There was a significant positive correlation between Dmin values and plasma CC16 levels (P = .012). In the case–control study, the 38AA + AG genotype was significantly associated with late-onset asthma (onset at >40 years; odds ratio, 1.63; P = .016). ConclusionThese results suggest that the CC16 A38G polymorphism may play a role in asymptomatic AHR and contribute to the development of late-onset asthma.

Increased Asymptomatic Airway Hyper-Responsiveness in Obese Individuals

Objective. Asymptomatic airway hyper-responsiveness (AHR) represents a risk of further accelerated decline in lung function, and of asthma. Due to the fact that rare and contradictory results exist concerning the impact of obesity on BHR, we re-assessed the prevalence of bronchial hyper-responsiveness (BHR) in a large cohort of 60 lean, 84 overweight, and 360 class 1–3 obese non-asthmatic individuals, by coupled plethysmography and spirometry. Methods. Baseline-specific airway conductance (SGaw) and spirometric values were measured and then a methacholine challenge testing (MCT) was performed and considered as positive when a ≥200% increase in specific airway resistance (SRaw = 1/SGaw) was reached. Results. Compared to lean and overweight subjects, obese subjects of any class presented about a twice more frequent AHR (∼ 50% in obese vs. 17 and 26% in lean and overweight subjects, respectively). However, the bronchial sensitivity (methacholine dose doubling SRaw) and the shape of the relationship between SGaw and cumulative methacholine doses were the same in the five groups of individuals. Conclusion. The present data show a more frequent AHR in obese subjects. The association of plethysmography with spirometry, by taking into account the bronchodilator effect of the lung inflation (preceding the expiratory flow measurement) in some individuals, permitted to include some MCT which would have been otherwise excluded.

Cross-Sectional Assessment of the Roles of Comorbidities in Resting and Activity-Related Dyspnea in Severely Obese Women

Objectives. Obesity has been associated with a lesser degree of asthma control that may be biased by other comorbidities. The objectives of this cross-sectional study were to describe resting and activity-related dyspnea complaints according to the presence of obesity-related comorbidities (asymptomatic airway hyperresponsiveness (AHR), asthma, gastroesophageal reflux disease (GERD) and sleep-disordered breathing (SDB)). We hypothesized that obese women can exhibit both resting and activity-related dyspnea, independently of the presence of asthma. Methods. Severely obese (body mass index (BMI) > 35 kg m−2) women prospectively underwent description of resting and activity-related dyspnea (verbal descriptors and Medical Research Council (MRC) scale), pulmonary function testing (spirometry, absolute lung volumes, and methacholine challenge test), oesogastro-duodenal fibroscopy, and overnight polygraphy. Thirty healthy lean women without airway hyperresponsiveness were enrolled. Results. Resting dyspnea complaints were significantly more prevalent in obesity (prevalence 41%) than in healthy lean women (prevalence 3%). Chest tightness and the need for deep inspirations were independently associated with both asthma and GERD while wheezing and cough were related to asthma only in obese women. Activity-related dyspnea was very prevalent (MRC score > 1, 75%), associated with obesity, with the exception of wheezing on exertion due to asthma. Asymptomatic AHR and SDB did not affect dyspneic complaints. Conclusions. In severely obese women referred for bariatric surgery, resting dyspnea complaints are observed in association with asthma or GERD, while activity-related dyspnea was mainly related to obesity only. Consequently, asthma does not explain all respiratory complaints of obese women.

Phenotypic differences between asymptomatic airway hyperresponsiveness and remission of asthma

The present study aimed to illustrate differences in characteristics and perception of dyspnea between young atopic adults who have no history of asthma (never-asthmatics) with or without asymptomatic airway hyperresponsiveness (AHR) and those who had childhood asthma and consider themselves to be grown out of the disease (past-asthmatics). Blood parameters, lung function and methacholine PC(20) were measured in 88 never-asthmatics and 24 past-asthmatics. A perception score of dyspnea at 20% fall in FEV(1) (PS(20)) was obtained by interpolation of the two last points on the perception (modified Borg scale)/fall in FEV(1) curve during methacholine challenge. Thirty-one of 88 never-asthmatics and eighteen of 24 past-asthmatics exhibited AHR (PC(20) was <8mg/ml). Higher levels of specific IgE to house dust mite in past-asthmatics were observed than never-asthmatics with and without AHR. Mean values of FEV(1) and FEF(25-75) (%predicted) were significantly lower in past-asthmatics than never-asthmatics without AHR, and the values in never-asthmatics with AHR were intermediate between never-asthmatics without AHR and past-asthmatics. PC(20) was not significantly different between past-asthmatics and never-asthmatics with AHR. Of particular interest was that PS(20) was significantly lower in never-asthmatics with AHR compared with past-asthmatics. The present findings suggest the possibilities that presence or absence of past history of outgrow of childhood asthma might be associated with airway narrowing, sensitization to house dust mite and perception of dyspnea in young asymptomatic adults with atopy and AHR.

Are asymptomatic airway hyperresponsiveness and allergy risk factors for asthma? A longitudinal study

To the Editors: We read with interest the recent paper by van den Nieuwenhof et al. 1 who reported no statistically significant association of airway hyperresponsiveness (AHR) with asthma incidence over 14 yrs in 123 asymptomatic adolescents aged 10–22 yrs at baseline. They concluded that AHR is not a risk factor for the development of asthma in adulthood and that screening for AHR in adolescents to detect subjects at risk for asthma cannot be recommended. We similarly assessed the association between AHR at baseline and asthma incidence over 11.4 yrs among 172 asymptomatic children (44.2% with AHR (provocative dose causing a 20% fall in forced expiratory volume in one second <4 mg methacholine) at baseline) and 517 adults (31.7% with AHR at baseline) from the Epidemiological Study on the Genetics and Environment of Asthma (EGEA) 2, 3. Asymptomatic adults were defined as those with a null symptomatic score according to Pekkanen et al. 4 over the previous 12 months. The score is based on asthma-like symptoms (wheeze with breathlessness, woken with chest tightness, attack of shortness of breath (SOB) at rest, attack of SOB after …

Asymptomatic airway hyperresponsiveness: what does it mean?

To the Editors: I read with interest the study by van den Nieuwenhof et al. 1, which appeared in a recent issue of the European Respiratory Journal . The study’s conclusion is certainly of interest: screening for asymptomatic airway hyperresponsiveness (AHR) in adolescents does not identify subjects at risk of developing asthma, whilst the presence of allergy is a risk factor for asthma. However, the observations leading to this statement should be interpreted with caution. I agree with the authors that AHR may be variable. It can improve significantly at adolescence, the period associated with the highest incidence of asthma remission. The situation seems different in adults, however. In some subjects, AHR may reflect a previous “insult” to the airways, either of infectious, toxic or allergic origin, or it could be the consequence …

Are asymptomatic airway hyperresponsiveness and allergy risk factors for asthma? A longitudinal study

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but it is unclear whether asymptomatic AHR is associated with a higher risk of asthma. The present study assessed whether there is an association between asymptomatic AHR in adolescence and asthma in adulthood. The association between allergy and development of asthma was also investigated. A follow-up study of a general population cohort of adolescents was performed 14 yrs after baseline. Respiratory status was assessed at baseline in 1989 and at follow-up in 2003-2004 by a respiratory symptoms questionnaire, spirometry and histamine challenge. Allergy status was also assessed. The respiratory status of 199 subjects was assessed twice. In total, 91 (46%) subjects had the same AHR status in combination with respiratory symptoms at follow-up as at baseline. Adjusted for age, sex, allergy, family history of asthma and smoking history, having asymptomatic AHR was not significantly related to having asthma 14 yrs later (odds ratio (OR) 2.15, 95% confidence interval (CI) 0.67-6.83). For subjects with allergy at baseline, the OR for developing asthma was 4.45 (95% CI 1.46-13.54). Screening for asymptomatic airway hyperresponsiveness in adolescence does not identify subjects at risk of developing asthma. Conversely, the presence of allergy in adolescence does seem to be a risk factor for asthma development.

Atopy May Be an Important Determinant of Subepithelial Fibrosis in Subjects with Asymptomatic Airway Hyperresponsiveness

The bronchial pathology of asymptomatic airway hyperreponsiveness (AHR) subjects is not well understood, and the role of atopy in the development of airway remodeling is unclear. The aim of this study was to evaluate whether atopy is associated with airway remodeling in asymptomatic AHR subjects. Five groups, i.e., atopic or non-atopic subjects with asymptomatic AHR, atopic or non-atopic healthy controls, and subjects with mild atopic asthma, were evaluated by bronchoscopic biopsy. By electron microscopy, mean reticular basement membrane (RBM) thicknesses were 4.3±1.7 µm, 3.4±1.8 µm, 2.5±1.5 µm, 2.6±1.1 µm, and 2.3±1.2 µm in the mild atopic asthma, atopic and non-atopic asymptomatic AHR, atopic and non-atopic control groups, respectively (p=0.002). RBM thicknesses were significantly higher in the mild atopic asthma group and in the atopic asymptomatic AHR group than in the other three groups (p=0.048). No significant difference in RBM thickness was observed between the atopic asymptomatic AHR group and the mild atopic asthma group (p>0.05), nor between non-atopic asymptomatic AHR group and the two control groups (p>0.05). By light microscopy, subepithelial layer thicknesses between the groups showed the same results. These findings suggest that RBM thickening occurs in subjects with atopic asymptomatic AHR, and that atopy plays an important role in airway remodeling.

Lung hyperinflation, perception of bronchoconstriction and airway hyperresponsiveness

To compare the influence of underlying airway inflammation and lung hyperinflation on dyspnea during induced bronchoconstriction in subjects with mild asthma (or asymptomatic airway hyperresponsiveness (AAHR). Fourteen mild asthmatic and 14 AAHR subjects had methacholine and 5'-adenosine monophosphate (AMP) challenges, and induced sputum analysis. Changes in inspiratory capacity (IC) and respiratory symptom scores were measured after challenges. Perception of respiratory symptoms was recorded on a modified Borg scale. The mean baseline FEV1, IC, mean provocative concentration of methacholine inducing a 20% decrease in FEV1 (PC20), the mean PC20 AMP and median inflammatory cell counts were similar in both groups. After methacholine, mean (+/-SD) reductions in FEV1 were 24.7+/-10.3% in mild asthma and 35.6+/-19.1% in AAHR (P>0.05); reductions in IC were, respectively, 10+/-12% and 24+/-20% (P>0.05); mean breathlessness scores at PC20 were 1.1 in mild asthma and 0 in AAHR P=0.003), and mean chest tightness scores were 1.2 in mild asthma and 0.8 in AAHR (P>0.05). Maximum chest tightness scores following MC correlated with the maximum decrease in IC in mild asthma (rs=0.75,P=0.009) and with the maximum decrease in FEV1 in AAHR (rs=0.60,P=0.04). After AMP, symptom scores were not significantly correlated with decreases in FEV1 or IC. The number of inflammatory cells was not correlated with decreases in IC after methacholine, AMP or with their PC20s, although inflammation was minimal in both groups. Lower breathlessness scores in AAHR compared to mild asthma were not explained by differences in lung hyperinflation nor in airway inflammation.

Response to mannitol in asymptomatic subjects with airway hyper‐responsiveness to methacholine

Bronchial provocation using methacholine, a cholinergic agonist, causes airway narrowing directly by contraction of bronchial smooth muscle. While methacholine has a high sensitivity for identifying airway hyper-responsiveness (AHR), it does not have a high specificity to diagnose asthma and false-positive responses may be observed in non-asthmatics. Mannitol is an osmotic stimulus that acts indirectly to cause airway narrowing by release of endogenous bronchoconstricting mediators. We tested the hypothesis that subjects with asymptomatic AHR to methacholine would not have AHR to mannitol. Sixteen subjects with a methacholine PD(20) <8 micro mol were challenged with mannitol. A positive response to mannitol was defined as a 15% decline in forced expiratory volume in 1 s (FEV(1)) after <635 mg (PD(15)). Expired nitric oxide (eNO) and blood eosinophils were also measured. The GM PD(20) for methacholine was 2.25 micro mol [95% confidence interval (CI): 2.19-5.29], the mean eNO was 14.7 p.p.b. (CI: 10.1-19.4) and the eosinophil count was 0.20 x 10(-9)/L (CI: 0.14-0.27 x 10(-9)/L). Only one subject (a smoker, 10 pack-years, FEV(1) 76% pred, non-allergic rhinitis, normal eNO and eosinophil count) also had a mild positive response to mannitol (PD(15): 451 mg). The response to mannitol was within the normal range in asymptomatic subjects with AHR to methacholine. Further evidence on the responsiveness to mannitol compared with methacholine in a random population sample is required to elucidate whether mannitol is a more specific test for diagnosing asthma.

Association Between Nonspecific Airway Hyperresponsiveness and Arg16Gly β2-Adrenergic Receptor Gene Polymorphism in Asymptomatic Healthy Japanese Subjects

Nonspecific airway hyperresponsiveness (AHR), a cardinal feature of asthma, is thought to result from several genetic and environmental factors. Asymptomatic AHR in nonasthmatic healthy subjects might be a risk factor for the development of asthma. Genetic variations in codons 16 and 27 of the human beta(2)-adrenergic receptor (beta(2)-AR) alter receptor function in vitro and are associated with various asthma-related phenotypes, including asthma severity and AHR. To date, however, few reports have examined the impact of beta(2)-AR gene polymorphism on AHR in asymptomatic healthy subjects.To determine whether polymorphism of the beta(2)-AR gene (Arg16Gly and Gln27Glu) might influence nonspecific AHR in asymptomatic healthy Japanese subjects.A cohort of 120 asymptomatic healthy subjects was analyzed using a stepwise linear regression model. Nonspecific airway responsiveness was measured using a continuous methacholine inhalation method (Astograph; Chest; Tokyo, Japan). We used values of the cumulative dose of inhaled methacholine measured at the inflection point at which respiratory conductance starts to decrease (Dmin) as an index of AHR. Genotyping to identify polymorphisms at codons 16 and 27 was conducted using an assay combining kinetic real-time quantitative polymerase chain reaction with allele-specific amplification.The Gly16Gly genotype was associated with lower Dmin values. The log Dmin value of asymptomatic healthy subjects carrying the Arg16 allele (Arg16/Arg or Arg16/Gly, n = 90) was 1.09 +/- 0.56 (mean +/- SD), while those homozygous for the Gly16 allele (n = 30) yielded a log Dmin value of 0.85 +/- 0.56 (p < 0.05).This study indicates that a specific beta(2)-AR polymorphism at codon 16 might be a genetic determinant of AHR, as judged by methacholine-induced bronchoconstriction in asymptomatic healthy subjects.

Outcome in adulthood of asymptomatic airway hyperresponsiveness to histamine and exercise-induced bronchospasm in childhood

Studies of the clinical outcome in adulthood of asymptomatic airway hyperresponsiveness (AHR) to histamine or exercise-induced bronchospasm (EIB) detected in childhood in general population samples are sparse and have produced conflicting results. To describe the outcome of asymptomatic AHR to histamine and EIB. Data from a 12-year follow-up study of a random population sample of individuals aged 7 to 17 years at enrollment were analyzed; only individuals without asthma at enrollment were included in the analysis. AHR to inhaled histamine, EIB, lung function, and sensitization to aeroallergens were measured. Among the 281 nonasthmatic participants studied, 58 (22%) had AHR to histamine, 33 (12%) had EIB, and 82 (29%) had AHR to histamine and/or EIB. At follow-up, 37.9% of individuals with AHR to histamine and 30% of individuals with EIB had developed current asthma, compared with only 5% of individuals in whom these test results were negative. In patients with AHR to histamine, parental asthma (odds ratio [OR], 12.6; 95% confidence interval [CI], 1.5-108.5), furred pets ownership (OR, 6.0; 95% CI, 1.2-19.6), and dermatitis and/or rhinitis in childhood (OR, 2.2; 95% CI, 1.1-5.1) predicted the subsequent development of asthma, whereas no risk factors for the development of asthma could be identified in individuals with EIB CONCLUSION: Asymptomatic AHR to histamine and EIB in childhood predict the subsequent development of asthma in adulthood. A genetic disposition to asthma, furred pets ownership, and concomitant rhinitis or dermatitis increase the risk of asthma development in individuals with AHR to histamine.

Clinical features and airway inflammation in mild asthma versus asymptomatic airway hyperresponsiveness

We still do not know why some subjects with airway hyperresponsiveness (AHR) experience no respiratory symptoms. Our aim was to compare pulmonary function, perception of bronchoconstriction, and airway inflammation in atopic subjects with mild recently diagnosed (<5 years, n=30) or longer-standing (5 years or more, n=30) symptomatic asthma in comparison with atopic subjects with asymptomatic AHR (n=27). All subjects had measurements of expiratory flows, PC(20) methacholine, perception of breathlessness and induced sputum cell differential, eosinophil cationic protein and alpha(2)-macroglobulin levels. Compared with the other groups, PC(20) was significantly lower in longer-standing asthma and perception score for breathlessness at 20% fall in FEV(1) was lower in asymptomatic subjects. Markers of airway inflammation were similar in all groups. There were no significant correlations between sputum eosinophils, alpha(2)-macroglobulin and/or eosinophil cationic protein levels and FEV(1), FVC or PC(20) in either group. Subjects with mild asthma or asymptomatic AHR are similar in regard to induced sputum markers of airway inflammation. Although perception of bronchoconstriction was slightly lower in asymptomatic subjects, additional factors are probably involved to explain why they report no respiratory symptoms. Further studies are needed to determine why these last are asymptomatic.

Interleukin‐4 production by human alveolar macrophages

IL-4 is a key factor for T helper type 2 (Th2) differentiation and Ig class switching to IgE and IgG(4) during the development of immune responses. IL-4 is produced by T cells, mast cells, basophils, and eosinophils. However, there is also evidence suggesting that rat alveolar macrophages (AMs) produce IL-4. Given the importance of AMs and Th2-related diseases in the lung, we investigated the production of IL-4 by human AMs. Human AMs were isolated from bronchoalveolar lavage, purified, and IL-4 production was investigated at mRNA and protein levels using real-time PCR, flow cytometry, immunocytochemistry, and ELISA. The presence of IL-4 was investigated in subjects with asthma or asymptomatic airway hyper-responsiveness, and in normal non-smokers. IL-4 and IL-4delta2 (a splice variant found in other IL-4 producing cells) mRNAs were found in all these subjects, but IL-4 expression could not be correlated with a particular disease. Protein production was verified by immunocytochemistry and flow cytometry analysis demonstrating, respectively, up to 69% and 59% positive AMs, regardless of the subject condition. Furthermore, phorbol-12-myristate-13-acetate and calcium ionophore stimulated the release of IL-4 after 48 h treatment in the presence of anti-IL-4 receptor antibody. Our results show for the first time that IL-4 and IL-4delta2 mRNA are expressed and IL-4 protein produced and released by human AMs, suggesting a contribution of these cells in the modulation of Th2 immune response.

Clinical features and airway inflammation in mild asthma vs asymptomatic airway hyperresponsiveness

Clinical features and airway inflammation in mild asthma vs asymptomatic airway hyperresponsiveness