Presence Of Bronchial Hyperresponsiveness Research Articles

Role of bronchial hyperresponsiveness in patients with obstructive sleep apnea with asthma-like symptoms

BackgroundObstructive sleep apnea (OSA) is one of the major co-morbidities and aggravating factors of asthma. In OSA-complicated asthma, obesity, visceral fat, and systemic inflammation are associated with its severity, but the role of bronchial hyperresponsiveness (BHR) is unclear. We investigated the involvement of BHR and mediastinal fat width, as a measure of visceral fat, with OSA severity in patients with OSA and asthma-like symptoms. MethodsPatients with OSA who underwent BHR test and chest computed tomography scan for asthma-like symptoms were retrospectively enrolled. We evaluated the relationship between apnea–hypopnea index (AHI) and PC20 or anterior mediastinal fat width, stratified by the presence or absence of BHR. ResultsOSA patients with BHR (n = 29) showed more obstructive airways and frequent low arousal threshold and lower mediastinal fat width, and tended to show fewer AHI than those without BHR (n = 25). In the overall analysis, mediastinal fat width was significantly positively correlated with AHI, which was significant even after adjustment with age and gender. This was especially significant in patients without BHR, while in OSA patients with BHR, there were significant negative associations between apnea index and airflow limitation, and hypopnea index and PC20. ConclusionsRisk factors for greater AHI differed depending on the presence or absence of BHR in OSA patients with asthma-like symptoms. In the presence of BHR, severity of asthma may determine the severity of concomitant OSA.

Inflammatory Phenotypes of Cough Variant Asthma as Response Predictors to Anti-Asthmatic Therapy.

BackgroundEosinophilic inflammatory phenotype was thought to be the most common phenotype of cough variant asthma (CVA), nevertheless other phenotypes were also reported.PurposeThe study aimed to analyze the inflammatory phenotypes of CVA in relation to treatment response to the stepwise anti-asthmatic treatment.Patients and MethodsThe study included 45 patients with chronic cough (CC) and suspicion of CVA (normal chest X-ray, presence of bronchial hyperresponsiveness and no history of wheezing or dyspnea) in whom induced sputum was successfully collected. Based on the cellular composition of the sputum, patients were divided into major inflammatory phenotypes: eosinophilic, neutrophilic, paucigranulocytic or mixed granulocytic. A stepwise treatment, including inhaled corticosteroids with long-acting β2-agonist, montelukast and short-term therapy with prednisone was initiated. Good treatment response was defined as the reduction in cough severity at least 20 mm from the baseline in visual analogue scale and improvement in cough-related quality of life assessed by the Leicester cough questionnaire at least 1.3 points after any of three steps.ResultsFinally, 40/45 (88.9%) patients improved after therapy. Eosinophilic asthma was found in 13/40 (32.5%) patients, neutrophilic in 6/40 (15.0%) and paucigranulocytic pattern in 21/40 (52.5%) patients. No one demonstrated a mixed granulocytic phenotype. The response to the treatment was similar in all groups. However, the reduction in cough severity was inversely related to the percentage of sputum neutrophils (r = −0.44, P = 0.003). We showed that the percentage of neutrophils in sputum >46% may be considered as a predictor of poor response to anti-asthmatic therapy.ConclusionThe diversity of inflammatory phenotypes with paucigranulocytic preponderance was found in subjects with CVA. The response to anti-asthmatic treatment in patients with CVA was not related to the inflammatory phenotype. High neutrophil count in sputum may predict poor response to anti-asthmatic therapy in patients with CC and bronchial hyperresponsiveness.

Accuracy of spirometry for detection of asthma: a cross-sectional study.

Asthma is a chronic inflammatory disease with airway hyperresponsiveness. Spirometry is the most commonly used test among asthmatic patients. Another functional test used for diagnosing asthma is the bronchial challenge test. The aim of this study was to analyze the accuracy of spirometry for detecting asthma in the general population. Cross-sectional study with data analysis to evaluate the accuracy of spirometry through calculating sensitivity, specificity and predictive values and through the kappa agreement test. Subjects who constituted a birth cohort were enrolled at the age of 23 to 25 years. Spirometric abnormality was defined as reduced forced expiratory volume in one second, i.e. lower than 80% of the predicted value. Measurement of bronchial responsiveness was performed by means of the bronchial challenge test with methacholine. The gold-standard diagnosis of asthma was defined as the presence of bronchial hyperresponsiveness in association with respiratory symptoms. Asthma was detected in 200 subjects (10.4%) out of the sample of 1922 individuals. Spirometric abnormality was detected in 208 subjects (10.9%) of the sample. The specificity of spirometric abnormality for detecting asthma was 90%, sensitivity was 23%, positive predictive value was 22%, and negative predictive value was 91%. The kappa test revealed weak agreement of 0.13 (95% confidence interval, CI: 0.07-0.19) between spirometry and the diagnosis of asthma. Spirometry, as a single test, has limitations for detecting asthma in the general population.

Obstrüktif uyku apne sendromu tanılı hastalarda bronş hiperreaktivitesi

The relationship between obstructive sleep apnea syndrome (OSAS) and bronchial hyperresponsiveness (BHR) is not well known. In this study, we investigated the association between BHR and disease severity in patients with OSAS. Fourty seven (37 male/10 female) OSAS patients admitted with polysomnography enrolled to the study. Histamine bronchial challenge test was performed and body mass index (BMI, kg/m2) was calculated. Presence of BHR was diagnosed as positivity of bronchial provocative test (BPT) (PD values ≤ 16 mg/mL). Patients were questioned with Epworth sleepiness scale (ESS). Histamine bronchial challenge test was positive in 21 of 47 patients. There were significant negative correlations between PD 20 value and AHI (r= -0.47, p= 0.03), BMI (r= -0.45, p= 0.03), and ESS score (r= -0.45, p= 0.03) in the patients with BHR. In addition, AHI (p= 0.03), BMI (p= 0.02), ESS scores (p= 0.03) were higher in patients with BHR (21 patients) than in patients not having BHR (26 patients). Significant negative relation was found between PD 20 value and AHI (b=-0.45, p= 0.03) and significant positive relation was found between presence of BHR and AHI (p= 0.04), BMI (p= 0.03) independently of age and sex in multiple regression analysis. BHR is common in patients with OSAS. As severity of OSAS increased, severity of BHR increased. In addition, obesity may trigger presence of BHR in patients with OSAS.

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.

Feasibility and acceptability of using bronchial hyperresponsiveness to manage asthma in primary care: a pilot study

To determine if indirect testing for bronchial hyperresponsiveness (BHR) to monitor inhaled corticosteroid (ICS) treatment in asthma is feasible and acceptable in primary care. Fourteen adult patients with asthma aged 22-70 years (4M:10F, forced expiratory volume in 1 s >70% predicted) taking ICS performed a test for BHR using mannitol on three visits 6 weeks apart. ICS dose adjustments were made based on the presence of BHR. The Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire were used at each visit. A semi structured interview at study exit assessed subject acceptability. BHR did not return in those with no BHR at study entry (n=9) with decreasing ICS dose. Improvements in BHR with increasing ICS dose (n=5) were observed with clinically significant improvements in AQLQ (mean score increase >0.5, p=0.02). Feasibility and acceptability of BHR testing was demonstrated. It is feasible and acceptable to perform BHR testing using mannitol to help identify patients with asthma who would benefit from ICS dose increases and those with no BHR who could have a dose reduction. Australia New Zealand Clinical Trial Registry ACTRN12610000807055.

Population-based study of multiplexed IgE sensitization in relation to asthma, exhaled nitric oxide, and bronchial responsiveness

IgE sensitization is an important risk factor for the development of asthma. The aim of this study was to investigate the IgE antibody profile for a broad spectrum of allergen molecules in asthmatic patients. Participants from the European Community Respiratory Health Survey II (n=467) were tested with ImmunoCAP ISAC against 103 allergen molecules. The presence of bronchial hyperresponsiveness was measured with a methacholine challenge test and bronchial inflammation with fraction of exhaled nitric oxide (Feno). A total of 38% of the controls and 72% of the asthmatic patients were sensitized against at least 1 of the allergen components (P<.0001). Asthma was independently related to having IgE antibodies against pollen (odds ratio=2.2) and perennial airway allergens (odds ratio=5.6), increased Feno was independently related to having IgE antibodies against food allergens and perennial allergens, while bronchial responsiveness was independently associated with having IgE antibodies against only perennial allergens. Sensitization to food allergens was related to asthma and increased Feno if IgE antibody against pollen allergens was present. Simultaneous sensitization to perennial, pollen, and food allergens involves the highest risk of asthma (odds ratio=18.3), bronchial inflammation, and responsiveness. Feno, bronchial responsiveness, and the risk of asthma increase with multiple sensitizations to different allergen groups. We show for the first time that the presence of IgE antibodies against food allergens is independently associated with increased Feno and increases the risk of asthma in subjects with simultaneous sensitization to pollen allergens.

Sevoflurane and desflurane protect cholinergic-induced bronchoconstriction of hyperreactive airways in rabbits

The potential of desflurane to alter respiratory mechanics in the presence of bronchial hyperresponsiveness (BHR) is still a subject of debate. Accordingly, we evaluated the bronchoprotective potential of desflurane compared with sevoflurane following cholinergic lung constriction in rabbits with normal and hyperreactive airways. The input impedance of the respiratory system (Zrs) was measured during midazolam-based anesthesia before and during intravenous infusions of increasing doses of methacholine (MCh). The rabbits in the control group (Group C) were then randomized to receive either sevoflurane 1 MAC followed by desflurane 1 MAC or vice versa, whereas ovalbumin-sensitized rabbits received sevoflurane followed by desflurane (Group S-SD) or vice versa (Group S-DS). Baseline Zrs measurements and the MCh provocations were repeated under the maintenance of each volatile agent. Airway resistance (Raw), tissue damping (G), and elastance data were obtained from Zrs by model fitting. Similar bronchoprotective effects of sevoflurane and desflurane against MCh-induced bronchoconstriction were observed independently of the severity of the bronchospasm and the presence of BHR. With sevoflurane, the decreases in Raw ranged from 22 (8.8)% to 44 (12)%, and with desflurane, they ranged from 22 (8.7)% to 50 (12)%. The increases in G reflecting the enhanced ventilation heterogeneities in the lung periphery were not affected by the volatile agents. If the contractile stimulus is cholinergic in origin, sevoflurane and desflurane exert similar bronchoprotective potentials to act against lung constriction independent of the presence of BHR. These volatile anesthetics otherwise lack a potential to improve the enhanced ventilation heterogeneities that develop particularly in the presence of BHR.

Hiperrespuesta bronquial a la metacolina en niños menores de 4 años con bronquitis de repetición

Objective To evaluate bronchial hyperresponsiveness in children under 4 years of age with recurrent wheezing bronchitis, and to determine if its presence or absence can predict the subsequent progression to a transient or persistent wheezing bronchitis phenotype. Population and methods A bronchial challenge test was performed with methacholine using a modified tidal volume method, without sedation in a group of patients from 8 to 47 months of age with recurrent wheezing bronchitis and a control group of healthy children. A decrease in oxygen saturation of ≥5% or an increase in respiration rate of >50% [PCwheeze (PCw)] was considered a positive response. The patients were subsequently clinically followed up to assess their progress. Results A total of 63 patients and 16 controls were studied (mean age 23.9 vs. 25.2 months). The PCw was lower than the control group (≤4 mg/ml) in 43 (68%) children from the bronchitis group ( P<0.001). No significant adverse effects were observed on performing the test. After a mean follow up of 28.5 months, completed in 49 of the patients, no differences were seen between the presence of bronchial hyperresponsiveness at the beginning of the study and the subsequent progression to transient, infrequent and frequent wheezing ( P=0.63). Conclusions A high percentage of children under 4 years of age affected by wheezing bronchitis had a bronchial hyperresponse. The subsequent progression to transient or persistent wheezing bronchitis phenotype is not associated with bronchial hyperresponsiveness.

Association between Obesity and the Prevalence of Allergic Diseases, Atopy, and Bronchial Hyperresponsiveness in Korean Adolescents

Background: Although several mechanisms underlying the asthma-obesity connection have been proposed, debates still remain. This study was to determine whether overweight is associated with a higher prevalence of atopy, asthma symptoms, airway obstruction, bronchial hyperresponsiveness (BHR) or biomarkers of inflammation in a sample of Korean adolescents. Methods: We conducted a cross-sectional survey involving questionnaires, skin tests, spirometry and methacholine challenge tests among 717 adolescents from Seoul (South Korea). Overweight status was defined as a BMI greater than the local age- and gender-specific 85th percentile. Results: Overweight subjects more frequently reported ever having wheezing (24.6 vs. 14.0%, p = 0.001) and wheezing in the previous 12 months (11.5 vs. 6.3%, p = 0.02) than normal-weight subjects, especially in boys. Atopy was more common among overweight adolescents than among those of normal weight (61.5 vs. 49.2%, p = 0.002), especially in boys (65.0 vs. 52.8%, p = 0.005). Overweight subjects had higher total WBC counts and eosinophil counts, especially boys. The presence of BHR was more common only among overweight girls (32.8 vs. 18.0%, p = 0.028). Overweight status was a significant risk factor for the presence of atopy (odds ratio = 1.49; 95% CI 1.06–2.10), after adjusting for various confounders by logistic regression analysis. Conclusions: An association was found between overweight status and both atopy and an increased prevalence of wheezing in adolescent Korean boys. These findings suggest that being overweight in puberty may be one of several risk factors responsible for atopy, BHR, and asthma symptoms.

Bronchial Hyperresponsiveness to Methacholine in Children Under 4 Years with Recurrent Bronchitis

Objective To evaluate bronchial hyperresponsiveness in children under 4 years old with recurrent wheezing bronchitis, and to determine if its presence or absence can predict subsequent progression to a transient or persistent wheezing bronchitis phenotype. Population and methods A bronchial challenge test was performed with methacholine using a modified tidal volume method without sedation, in a group of patients from 8 to 47 months of age with recurrent wheezing bronchitis and a control group of healthy children. A decrease in oxygen saturation of ≥5% or an increase in respiration rate of >50% [PCwheeze (PCw)] was considered a positive response. The patients were subsequently clinically followed up to assess their progress. Results A total of 63 patients and 16 controls were studied (mean age 23.9 compared to 25.2 months). The PCw in 43 (68%) children from the bronchitis group was lower than the control group (≤4 mg/mL), ( P<.001). No significant adverse effects were observed on performing the test. After a mean follow-up of 28.5 months, completed in 49 of the patients, no differences were seen between the presence of bronchial hyperresponsiveness at the beginning of the study and the subsequent progression to transient, infrequent or frequent wheezing ( P=.63). Conclusions A high percentage of children under 4 years old with wheezing bronchitis had a bronchial hyperresponse. Subsequent progression to transient or persistent wheezing bronchitis phenotype is not associated with bronchial hyperresponsiveness.

Superoxide dismutases, lung function and bronchial responsiveness in a general population

Oxidative stress is an important causative factor in the onset and progression of smoking-related lung diseases, such as chronic obstructive pulmonary disease (COPD). Superoxide dismutases (SODs) can prevent an increase in oxidative burden. A total of 1,390 subjects from the prospective Vlagtwedde-Vlaardingen cohort were genotyped for two single nucleotide polymorphisms (SNPs) in SOD2 and four SNPs in SOD3, which were further analysed for associations with the presence of bronchial hyperresponsiveness (BHR; provocative concentration causing a 10% fall in the forced expiratory volume in one second (FEV(1); PC(10) <or=8 mg mL(-1) of histamine), COPD (defined as Global Initiative for Chronic Obstructive Lung Disease stage II or higher), lung function level and the longitudinal course of FEV(1). The intronic C5774T SNP of SOD2 was significantly associated with the presence of COPD and BHR in the total population. The T/T genotype for this polymorphism and the Val/Val genotype for the SOD2 Ala16Val substitution were risk factors for BHR in individuals without COPD. The SOD3 Arg213Gly substitution was associated with slower FEV(1) decline in never-smokers exclusively, and the SOD3 G(-4466)T SNP was associated with a lower vital capacity level. Both SOD2 polymorphisms are associated with bronchial hyperresponsiveness, a risk factor for chronic obstructive pulmonary disease, while SOD2 C5774T additionally confers a risk for chronic obstructive pulmonary disease in the total population. The current authors furthermore confirm previously reported associations of SOD3 single nucleotide polymorphisms with lung function in the general population.

Bronchial hyper-responsiveness and exhaled nitric oxide in chronic obstructive pulmonary disease.

Several lung diseases including asthma and chronic obstructive pulmonary disease (COPD) involve chronic inflammation of the airways. Therefore, there is great interest in non-invasive methods assessing airway inflammation. Measurement of bronchial hyper-responsiveness (BHR) and exhaled nitric oxide (NO) are such indirect markers of airway inflammation. Additional information about severity of disease, prognosis and possible response to anti-inflammatory treatment with inhaled corticosteroids can be gained by these methods. However, they are not yet established in assessing patients with COPD in clinical routine. BHR has long been recognised as a hallmark of asthma. Less is known about prevalence and clinical relevance of BHR in the general population and in COPD patients. Longitudinal studies have shown that BHR in healthy persons is a risk factor for development of respiratory symptoms, asthma and COPD. BHR has also been shown to increase the detrimental effect of cigarette smoke and is associated with a decline in lung function. Furthermore, studies indicate that the presence of BHR is a prognostic factor in COPD. Increased BHR to histamine has been shown to be a predictor for mortality in COPD patients. Based on current guidelines, treatment of patients with severe COPD (GOLD stage III and IV) and regular exacerbations includes therapy with inhaled corticosteroids. Inhaled corticosteroids have been shown to reduce frequency of exacerbations but they have not been shown to modify long-term decline in FEV1. However, one small study found that BHR to inhaled mannitol could possibly predict responsiveness to inhaled corticosteroids in patients with moderately severe COPD and identify a subgroup of patients that is likely to benefit from this treatment. Exhaled NO has been shown to correlate with other inflammatory markers and to be elevated in asthma. In COPD patients, data is inconsistent. However, measuring exhaled NO may have a role in the identification of patients with severe, unstable COPD who were shown to have higher NO levels compared to patients with stable COPD. This suggests that exhaled NO might be a method to assess and monitor disease activity in COPD. Possible explanations for the contradictory results are different measurement techniques of exhaled NO and different smoking histories of patients in various studies. Smoking has been found to be a confounding factor by reducing NO levels significantly, an effect which might counteract the potentially increased exhaled NO due to airway inflammation. In conclusion, measuring BHR and exhaled NO in patients with COPD might provide additional information about disease severity, prognosis and possible response to anti-inflammatory medical treatment. However, to establish these methods in clinical routine in COPD patients, more data is clearly needed.

Mast cell regulation of airway smooth muscle function in asthma

Asthma is a common disease affecting ≤10% of the adult Western population 1, 2. It is characterised by the presence of variable and potentially reversible airflow obstruction, which occurs as the result of bronchoconstriction, airway mucus plugging and airway oedema. Pathologically there is evidence of airway inflammation and remodelling 3–7. The mucosal inflammatory infiltrate commonly comprises activated T-cells, eosinophils and mast cells, while the accompanying structural changes include subepithelial collagen deposition, goblet cell- and mucous gland-hyperplasia, airway smooth muscle (ASM) hypertrophy and ASM hyperplasia. An important physiological feature of asthma is the presence of bronchial hyperresponsiveness (BHR) 8. This means there is an exaggerated bronchoconstrictor response of the ASM to direct and indirect stimuli such as histamine and exercise, respectively. While BHR is aggravated in the presence of classic allergic eosinophilic airway inflammation, it persists once this inflammation is controlled and is not present in patients with eosinophilic bronchitis 8, 9. This suggests that there is either a fundamental abnormality of ASM behaviour in asthmatic subjects or that there are interacting factors that have not been previously recognised. In support of the former, several phenotypic differences are evident in ASM cells cultured from the airways of asthmatic subjects. For example, when compared with normal ASM cells, cultured asthmatic ASM cells proliferate faster due to an altered pattern of matrix protein deposition 10, 11, secrete greater amounts of connective tissue-derived growth factor in response to transforming growth factor-β stimulation 12, and secrete markedly increased amounts of the chemokine CXCL10 in response to activation by cytokines 13. There is decreased expression of prostaglandin (PG)E2 by the asthmatic ASM 14, and proliferation of asthmatic ASM is not inhibited by corticosteroids due to impaired expression of the transcription factor CCAAT/enhancer …

Evaluation of the surgical treatment of nasal polyposis. II: Influence of a non-specific bronchial hyperresponsiveness

Conclusion. Bronchial hyperresponsiveness (BHR) is not a risk factor for surgery in patients with nasal polyposis (NP). Objective. Management of NP should be primarily medical, and surgery should not be envisaged before a trial of dual steroid therapy. In patients with severe NP resistant to a strict medical treatment, endoscopic sinus surgery is performed, but no prognostic factor for efficacy of surgery is obvious. Some authors suggest that asthma could be a major risk for ineffectiveness of surgery. The aim of this study was to evaluate whether the presence of BHR can be considered a risk factor for ineffectiveness of surgery. Subjects and methods. Surgery (with associated medical treatment) was evaluated over a mean follow-up period of 74 months. A total of 63 subjects without and 131 subjects with BHR were operated according to a standardized protocol. Results. The present study shows that combined surgery and corticosteroid therapy is effective in the treatment of severe NP, producing significant and long-term improvements in symptoms and in the size of nasal polyps. BHR did not influence the outcome. Moreover, the mean amount of prednisolone and beclomethasone necessary after surgery was similar in the two groups.

Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma

Sex hormones may contribute to the higher prevalence and severity of adult asthma in women compared with men. Sequence variants in the estrogen receptor alpha gene (ESR1) may alter estrogen action in asthma. Two hundred asthma probands and their families (n=1249) were genotyped for 5 single nucleotide polymorphisms (SNPs) in the ESR1 gene (intervening sequence 1 [IVS1]-1505A/G, IVS1-1415T/C, IVS1-397C/T, IVS1-351G/A and exon1+30T/C). Association with asthma and bronchial hyperresponsiveness (BHR) were tested. In the asthma probands, association of SNPs with BHR severity and annual FEV1 decline were determined. No SNP was associated with asthma. IVS1-397 was significantly associated with the presence of BHR (P=.02) and interacted with sex; female subjects with the CT or TT genotype were at risk (P=.01). In asthma probands, all SNPs were associated with FEV1 decline. Exon1+30 CT and TT group had an excess decline of 11.6 mL/y (P=.03) and 15.7 mL/y (P=.01), respectively, compared with the CC group. Of the IVS1 polymorphisms, IVS1-351G/A showed the strongest association, with the AA group having excess decline of 16.1 mL/y (P=.01) compared with the GG group. In subanalyses by sex, these associations were significant only in female subjects. ESR1 gene variants may affect development of BHR, particularly in female subjects. They may also lead to a more rapid lung function loss in patients with asthma, and in female subjects specifically. This may result from altered estrogen action, which affects lung development and/or airway remodeling. Further studies on ESR1 gene variations are important to understand better the origin of sex differences in asthma. Variations in the gene encoding estrogen receptor alpha are associated with BHR and a more rapid annual lung function decline, especially in female subjects. Even though this has no diagnostic or clinical implication, it may open avenues for future sex-specific treatment in asthma.

The Canadian Childhood Asthma Primary Prevention Study: Outcomes at 7 years of age

Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development. The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age. Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacholine inhalation tests, and allergy skin tests. At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV 1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71). The multifaceted intervention program was effective in reducing the prevalence of asthma in high-risk children at 7 years of age.

Genome screen in the French EGEA study: detection of linked regions shared or not shared by allergic rhinitis and asthma

In the sample of 295 French EGEA families with at least one asthmatic subject, a genome screen was conducted to identify potential linkage regions specific either to allergic rhinitis (AR) or to asthma as well as those shared by the two diseases. Two binary rhinitis phenotypes based on (1) diagnosis (ARbin1) and (2) symptoms (ARbin2) and a categorical ordered trait (ARcat) were considered. Asthma phenotype was based on answers to a standardized questionnaire plus the presence of bronchial hyper-responsiveness. Linkage analyses were conducted using the maximum likelihood binomial (MLB) method. These analyses provided potential evidence for linkage to three regions in the whole sample: 1p31 for the phenotype defined by ARbin2 plus asthma (P=0.00016), 2q32 for ARbin2 (P=0.00016) and 3p24-p14 for ARcat (P=0.001). Two other regions were detected in the subset of 185 families with at most one asthmatic sib: 9p22 and 9q22-q34 for ARbin1 (P=0.001 and 0.0007, respectively). No region showed evidence for linkage to asthma without being also linked to AR. While 1p31 may contain a genetic determinant common to asthma and AR, 2q32, 3p24-p14, 9p22 and 9q22-q34 are more likely to harbor genetic factors specific to AR.

Perinatal risk factors for bronchial hyperresponsiveness and atopy after a follow-up of 20 years

Background Perinatal risk factors are associated with lung function and respiratory symptoms in adult life. Whether the same holds for distinctive asthma features, such as bronchial hyperresponsiveness (BHR) and atopy, has scarcely been studied. Objective We sought to identify the perinatal risk factors for the development of BHR and atopy. Methods BHR and atopy were measured after 20 years' follow-up in 597 of 3162 babies born from 1975 through 1978. Factors directly related to delivery of these children were studied in association with the presence of BHR and atopy. Results Twenty-five percent had BHR, and 47% had atopy. Delivery duration of longer than 12 hours was associated with the development of atopy (odds ratio [OR], 2.24; 95% CI, 1.30-3.86), and severe respiratory infection in the first year of life was associated with the development of BHR (OR, 2.69; 95% CI, 1.41-5.16). Nonatopic subjects born after induced labor and current smokers were more likely to have BHR (ORs of 2.41 [95% CI, 1.07-5.41] and 2.50 [95% CI, 1.12-5.59], respectively). Prenatal smoke exposure and childhood pet keeping decreased the risk for atopy, especially in BHR-positive subjects (ORs of 0.51 [95% CI, 0.27-0.99] and 0.46 [95% CI, 0.24-0.88], respectively). Conclusions It has been shown that events before or during birth still have an effect on respiratory health 20 years later. We put forward that an extreme hormonal status during delivery primes the fetal immune system toward atopy development. Furthermore, a severe respiratory infection in the first year of life appears associated with BHR development, and prenatal smoke exposure might be protective for the development of atopy, yet explanatory mechanisms are lacking thus far.

Non-specific bronchial hyperresponsiveness is a risk factor for steroid insensitivity in nasal polyposis

ObjectiveManagement of nasal polyposis should be primarily medical. Resorting to intranasal ethmoidectomy should not be envisaged before a trial of dual steroid therapy. Nevertheless, no risk factor for steroid insensitivity in patients with nasal polyposis is actually defined. The aim of this study is to evaluate whether the presence of asthma and/or non-specific bronchial hyperresponsiveness (BHR) can be considered a risk factor for steroid insensitivity.Material and MethodsThis study focused on the evaluation of a dual modality, topical and systemic, over a follow-up period of 3 years. A total of 55 subjects with and 45 subjects without BHR were treated according to a standardized therapeutic protocol combining short-term oral administration of prednisolone and a daily intranasal spray of beclomethasone.ResultsOver the follow-up period of 3 years, this dual modality proved to be successful in 93.4% of subjects without BHR and without aspirin idiosyncrasy, in 82.2% of subjects with BHR and without aspirin idiosyncrasy and in 60% of subjects with BHR and aspirin idiosyncrasy. The percentage of patients who underwent surgery after the failure of medical treatment was significantly larger in patients with than without BHR (p<0.05) and in patients with than without aspirin idiosyncrasy (p<0.02).ConclusionThe presence of BHR and/or aspirin idiosyncrasy can be considered a major risk factor for steroid insensitivity in patients with nasal polyposis.