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Bronchial Hyperresponsiveness (bronchial + hyperresponsiveness)
Selected AbstractsBronchial hyperresponsiveness, atopy, and bronchoalveolar lavage eosinophils in persistent middle lobe syndromePEDIATRIC PULMONOLOGY, Issue 9 2006Kostas N. Priftis MD Abstract Most cases of middle lobe syndrome (MLS) in children are considered to be due to asthma and may recover spontaneously; however, in persistent MLS, repeated episodes of infection often institute a vicious cycle that may lead to persistent symptoms and bronchial hyperresponsiveness (BHR). The present study was undertaken to investigate whether asthma, as an underlying diagnosis, is predictive of a favorable outcome of children with persistent MLS. We evaluated 53 children with MLS who underwent an aggressive management protocol that included fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). These patients were compared to two other groups: one consisting of children with current asthma but no evidence of MLS (N,=,40) and another of non-asthmatic controls (N,=,42), matched for age and sex. Prevalence of sensitization (,1 aeroallergen) did not differ between patients with MLS and "non-asthmatics" but was significantly lower than that of "current asthmatics." A positive response to methacholine bronchial challenge was observed with increased frequency among children with MLS when compared to "current asthmatic" and non-asthmatic children. Multivariate logistic regression analysis revealed a positive correlation between an increased number of eosinophils in the BAL fluid (BALF) and a favorable outcome, whereas no correlation was detected between sensitization or BHR and BAL cellular components. In conclusion, children with MLS have an increased prevalence of BHR, even when compared to asthmatics, but exhibit prevalence of atopy similar to that of non-asthmatics. An increased eosinophilic BALF count is predictive of symptomatic but not radiographic improvement of MLS patients after aggressive anti-asthma management. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] The natural history of asthma from childhood to adulthoodINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2007M. S. Koh Summary Medical Practitioners are often questioned regarding the prognosis of a child with asthma. We have performed a literature review of the natural history of childhood asthmatics. Factors which affect the natural history and prognosis of childhood asthma are discussed. Current evidence suggests that evolution of asthma severity is fairly predictable. Features of childhood asthma such as severity, duration, atopy, bronchial hyperresponsiveness and exposure to smoking can predict the course of asthma into adulthood. Most children with mild intermittent asthma will outgrow their asthma, or have mild episodic asthma. Early commencement of anti-inflammatory therapy, such as inhaled corticosteroids may prevent the progression of the disease. Most patients with mild asthma have good functional outcome and low healthcare utilisation. [source] Risk factors of new-onset asthma in adults: a population-based international cohort studyALLERGY, Issue 8 2010J. M. Antó To cite this article: Antó JM, Sunyer J, Basagaña X, Garcia-Esteban R, Cerveri I, de Marco R, Heinrich J, Janson C, Jarvis D, Kogevinas M, Kuenzli N, Leynaert B, Svanes C, Wjst M, Gislason T, Burney P. Risk factors of new-onset asthma in adults: a population-based international cohort study. Allergy 2010; 65: 1021,1030 Abstract Background:, The occurrence of new-onset asthma during adulthood is common, but there is insufficient understanding of its determinants including the role of atopy. Objective:, To assess the risk factors for the development of new-onset asthma in middle-aged adults and to compare them according to atopy. Methods:, A longitudinal analysis of 9175 young adults who participated in two surveys of the European Community Respiratory Health Survey (ECRHS) conducted 9 years apart. Findings:, We observed 179 cases of new-onset asthma among 4588 participants who were free of asthma and reported at the beginning of the follow-up that they had never had asthma (4.5 per 1000 person-years). In a logistic regression, the following risk factors were found to increase the risk of new-onset asthma: female gender (OR: 1.97; 95% confidence interval (CI): 1.38,2.81), bronchial hyperresponsiveness (3.25; 2.19,4.83), atopy (1.55;1.08,2.21), FEV1 < 100 % predicted (1.87;1.34,2.62), nasal allergy (1.98;1.39,2.84) and maternal asthma (1.91;1.13;3.21). Obesity, respiratory infections in early life and high-risk occupations increased the risk of new-onset asthma although we had limited power to confirm their role. Among the atopics, total IgE and sensitization to cat were independently related to the risk of new-onset asthma. The proportion of new-onset asthma attributable to atopy varied from 12% to 21%. Conclusion:, Adults reporting that they had never had asthma were at a substantial risk of new-onset asthma as a result of multiple independent risk factors including lung function. Atopy explains a small proportion of new-onset adult asthma. [source] Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsivenessALLERGY, Issue 6 2009N. E. Reijmerink Introduction:,ADAM33 is the first identified asthma gene by positional cloning, especially asthma combined with bronchial hyperresponsiveness (BHR). Moreover, ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV1) in the general population. In utero and postnatal cigarette smoke exposure (CSE) are associated with reduced lung function, and development of BHR and asthma. We hypothesized that this may occur via interaction with ADAM33. Aim:, To replicate the role of ADAM33 in childhood lung function and development of BHR and asthma. Furthermore, we investigated gene,environment interaction of ADAM33 with in utero and postnatal CSE in the Dutch PIAMA cohort. Methods:, Six ADAM33 single-nucleotide polymorphisms (SNPs) were genotyped. Rint was measured at age 4 and 8 years, FEV1 and BHR at age 8 years; asthma was based on questionnaire data at age 8. Results:, In the total cohort, the rs511898 A, rs528557 C, and rs2280090 A alleles increased the risk to develop asthma (+BHR). There existed interaction between in utero but not postnatal CSE and the rs528557 and rs3918396 SNPs with respect to development of BHR, the rs3918396 SNP with Rint at age 8 and the rs528557 SNP with FEV1% predicted. Conclusions:, We confirm associations between ADAM33 and the development of asthma (+BHR). This is the first study suggesting that interaction of in utero CSE with ADAM33 results in reduced lung function and the development of BHR, which needs further confirmation. [source] Sputum eosinophilia: an early marker of bronchial response to occupational agentsALLERGY, Issue 5 2009O. Vandenplas Background:, False-negative responses to specific inhalation challenge (SIC) with occupational agents may occur. We explored whether assessing changes in sputum cell counts would help improve the identification of bronchial reactivity to occupational agents during SICs. Methods:, The predictive value of the changes in sputum cell counts after a negative FEV1 response to a first challenge exposure to an occupational agent was determined using the changes in airway calibre observed during repeated challenges as the ,gold standard'. The study included 68 subjects investigated for work-related asthma in a tertiary centre. After a control day, the subjects were challenged with the suspected occupational agent(s) for up to 2 h. All subjects who did not show an asthmatic reaction were re-challenged on the following day. Additional challenges were proposed to those who demonstrated a , 2% increase in sputum eosinophils or an increase in nonspecific bronchial hyperresponsiveness to histamine after the second challenge day. Results:, Six of the 35 subjects without changes in FEV1 on the first challenge developed an asthmatic reaction on subsequent challenges. ROC analysis revealed that a >3% increase in sputum eosinophils at the end of the first challenge day was the most accurate parameter for predicting the development of an asthmatic response on subsequent challenges with a sensitivity of 67% and a specificity of 97%. Conclusions:, An increase in sputum eosinophils is an early marker of specific bronchial reactivity to occupational agents, which may help to identify subjects who will develop an asthmatic reaction only after repeated exposure. [source] Predictors of bronchial hyperresponsiveness in chronic rhinosinusitis with nasal polypALLERGY, Issue 1 2009D. H. Han Background:, Chronic rhinosinusitis with nasal polyposis (CRSNP) and asthma are inflammatory lesions of the respiratory epithelium. This study was conducted to evaluate predictive factors of bronchial hyperresponsiveness (BHR) in patients with CRSNP. Methods:, BHR was evaluated using a methacholine bronchoprovocation test (MBPT) in 122 consecutive patients newly diagnosed with CRSNP at Seoul National University Hospital from January 2004 to June 2006. The following parameters were analyzed and compared between the BHR and non-BHR groups: symptoms, atopic status, current smoking, disease severity of CRSNP based on the Lund,Mackay scoring system of sinus CT, and counts of eosinophils in the serum and nasal tissues. Results:, Thirty-five percent of the patients were found to have BHR, and BHR was found to occur more frequently in patients that were currently suffering from sneezing (P = 0.007). In addition, the mean eosinophil counts of the serum and nasal tissues were higher in the BHR group than in the non-BHR group (P = 0.001 for the serum, P = 0.045 for the nasal tissues), and the eosinophil counts of the serum correlated to those of the nasal tissues (r = 0.334, P = 0.013). The disease severity, as determined by the Lund,Mackay scoring system, was not different between the two groups (P > 0.05). The best cutoff serum eosinophil count for predicting BHR in CRSNP patients was determined to be 300 cells/,l (sensitivity 70%, specificity 70%). Conclusion:, Taken together, these results indicate that moderate to severe sneezing and a serum eosinophil count , 300 cells/,l may be predictive factors for BHR in patients with CRSNP. [source] Omalizumab decreases nonspecific airway hyperresponsiveness in vitroALLERGY, Issue 2 2007P. Berger 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. [source] Relationship between adipokines and manifestations of childhood asthmaPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2008Kyung W. Kim Although the prevalences of asthma and obesity are increasing substantially in recent decades, very little is known about the possible association between them. We evaluated the roles of leptin, adiponectin, and resistin, which are adipokines produced by adipose tissue, on childhood asthma, and their association with pulmonary function and bronchial hyperresponsiveness. We studied 149 atopic asthmatic children, 37 non-atopic asthmatic children, and 54 healthy children. Body mass index was calculated using height and weight, which were measured on the same day that pulmonary function tests and methacholine challenge tests were performed. Skin prick tests were performed, and total eosinophil count, total serum immunoglobulin E (IgE), serum eosinophil cationic protein, leptin, adiponectin, and resistin were measured in all subjects. Atopic asthmatics had lower resistin levels compared with non-atopic asthma and control groups, but leptin and adiponectin did not show any difference among these three groups. Resistin demonstrated positive correlation with methacholine PC20 and negative correlations with eosinophil count and serum total IgE. Leptin and adiponectin showed associations with forced expiratory volume in 1 s or forced expiratory flow between 25,75%. Multiple regression analysis revealed that resistin was a significant predictive factor for asthma. There was no direct association between asthma and leptin or adiponectin. Our findings suggest that resistin may play a negative predictive role in asthma. Adiponectin and leptin showed close associations with pulmonary function and may have disease-modifying effects in children with asthma. [source] Increase in the prevalence of rhinitis among Danish children from 1986 to 2001PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2007Kåre Håkansson In recent decades, there has been a worldwide increase in the prevalence of atopic diseases. The aim of this study was to investigate whether there has been a change in the prevalence of rhinitis among children in Denmark from 1986 to 2001. We compared data from two random population-based samples of Danish children, aged 7,17 yr, who were examined in 1986 (n = 527) and 2001 (n = 480) using similar designs. Symptoms of rhinitis, skin test reactivity, and bronchial responsiveness to inhaled histamine were assessed. The prevalence of rhinitis increased from 11.8% in 1986 to 23.3% in 2001 (p < 0.001). The increase was most pronounced among subjects who suffered from non-allergic rhinitis (p < 0.001), and among subjects with severe symptoms (p < 0.001). The prevalence of asymptomatic positive skin prick test (SPT) decreased substantially (p < 0.001). A history of asthma and parental atopic disease were strong predictors of non-allergic rhinitis, whereas a history of asthma, parental atopic disease, bronchial hyperresponsiveness, eczema, and age at examination were statistically significant predictors of allergic rhinitis. The prevalence of non-allergic rhinitis among Danish children has increased substantially from 1986 to 2001. Furthermore, in general more severe symptoms of rhinitis were observed in 2001 compared with 1986. These results underline the importance of using objective measurements such as skin test reactivity when estimating time trends in the prevalence of allergic airways disease, as clinical interviews alone can be misleading. [source] Bronchial hyperresponsiveness, atopy, and bronchoalveolar lavage eosinophils in persistent middle lobe syndromePEDIATRIC PULMONOLOGY, Issue 9 2006Kostas N. Priftis MD Abstract Most cases of middle lobe syndrome (MLS) in children are considered to be due to asthma and may recover spontaneously; however, in persistent MLS, repeated episodes of infection often institute a vicious cycle that may lead to persistent symptoms and bronchial hyperresponsiveness (BHR). The present study was undertaken to investigate whether asthma, as an underlying diagnosis, is predictive of a favorable outcome of children with persistent MLS. We evaluated 53 children with MLS who underwent an aggressive management protocol that included fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). These patients were compared to two other groups: one consisting of children with current asthma but no evidence of MLS (N,=,40) and another of non-asthmatic controls (N,=,42), matched for age and sex. Prevalence of sensitization (,1 aeroallergen) did not differ between patients with MLS and "non-asthmatics" but was significantly lower than that of "current asthmatics." A positive response to methacholine bronchial challenge was observed with increased frequency among children with MLS when compared to "current asthmatic" and non-asthmatic children. Multivariate logistic regression analysis revealed a positive correlation between an increased number of eosinophils in the BAL fluid (BALF) and a favorable outcome, whereas no correlation was detected between sensitization or BHR and BAL cellular components. In conclusion, children with MLS have an increased prevalence of BHR, even when compared to asthmatics, but exhibit prevalence of atopy similar to that of non-asthmatics. An increased eosinophilic BALF count is predictive of symptomatic but not radiographic improvement of MLS patients after aggressive anti-asthma management. Pediatr Pulmonol. © 2006 Wiley-Liss, Inc. [source] Risk factors of bronchial hyperresponsiveness in children with wheezing-associated respiratory infectionPEDIATRIC PULMONOLOGY, Issue 1 2005Sitthivuddhi Futrakul MD Abstract The objectives of this study were to identify possible risk factors of bronchial hyperesponsiveness (BHR) in children up to 5 years of age with wheezing-associated respiratory infection (WARI), and to study the prevalence of BHR. Children up to 5 years of age with WARI were enrolled in the study. The parents or caregivers of children were asked about their demographic data and clinical histories. Physical examination and clinical score assessment were performed. Pulmonary function tests, i.e., tidal breathing flow volume (TBFV), were performed to measure tidal breathing parameters before and after salbutamol nebulization. If volume at peak tidal expiratory flow/expiratory tidal volume and time to peak expiratory flow/total expiratory time increased ,20%, or tidal expiratory flow at 25% of tidal volume/peak tidal expiratory flow increased ,20% after nebulization therapy, BHR was diagnosed. The number in the positive BHR group was used to calculate the prevalence of BHR, and clinical features were compared with those of the negative BHR group. Categorical data were analyzed for statistical significance (P,<,0.05) by chi-square test or Fisher's exact test, or Student's t -test, as appropriate. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for those with statistical significance. One hundred and six wheezing children underwent pulmonary function tests before and after salbutamol nebulization. With the aforementioned criteria, 41 cases (38.7%) were diagnosed with BHR. History of reactive airway disease, (OR, 6.31; 95% CI, 1.68,25), maternal history of asthma (OR, 3.45; 95% CI, 1.34,9), breastfeeding less than 3 months (OR, 3.18; 95% CI, 1.26,8.12), and passive smoking (OR, 3; 95% CI, 1.15,7.62) were significant risk factors of BHR. The eosinophil count was significantly higher in the BHR (+) group particularly, in children 1,5 years of age (P,,,0.01). Patchy infiltrates were more commonly found in patients with negative BHR but not statistically significant. In conclusion, a history of reactive airway disease, maternal history, breastfeeding less than 3 months, and passive smoking were significant risk factors for BHR. Pediatr Pulmonol. © 2005 Wiley-Liss, Inc. [source] Extrathoracic airway responsiveness in children with asthma-like symptoms, including chronic persistent coughPEDIATRIC PULMONOLOGY, Issue 3 2002Ipek Turktas MD Abstract Asthma-like symptoms, including chronic persistent cough, are not always specific for classical asthma. In order to investigate whether assessment of extrathoracic airway hyperresponsiveness (EAHR) during methacholine bronchial challenge helped in the evaluation of pediatric patients with asthma-like symptoms such as chronic cough, we examined 133 consecutive, unselected patients (mean age, 10.06,±,2.16 years) who had neither established asthma nor bronchial obstruction previously. We recorded the forced mid-inspiratory flow (FIF50) as an index of extrathoracic airway narrowing. In addition, a 25% decrease in FIF50 (PD25FIF50) below the cutoff concentration of ,,8 mg/mL methacholine was assumed to indicate EAHR. According to the methacholine response, 81 patients had EAHR, and 41 of them had combined EAHR and bronchial hyperresponsiveness (BHR); 39 patients had only BHR. Airway hyperresponsiveness was not demonstrated in 13 patients and not in any of the control children. When patients with cough as the sole presenting symptom (60.9%) were compared with those with cough and wheeze (20.3%), those with cough alone had a significantly greater probability of having EAHR (OR, 4.16; 95% CI, 1.32,13.13) and a lower probability of having BHR (OR, 0.70; CI, 0.25,1.95) than those with cough and wheeze. Patients with cough, wheeze, and dyspnea (18.8%) had a significantly greater chance of having BHR than those with cough alone (OR, 5.08; CI, 1.55,16.64). Patients with cough and wheeze as compared with those with cough, wheeze, and dyspnea had significantly greater probability of having both EAHR and BHR (OR, 4.71; CI, 1.94,11.47). In order to ascertain the clinical relevance of EAHR, we assessed in the second part of the study whether the effects of treatment of the underlying disease would result in relief of airway hyperresponsiveness. Rhinosinusitis and perennial allergic rhinitis accounted for EAHR in 71 patients, and 34 of them also demonstrated BHR. They received specific therapy for their upper airway diseases for 4 weeks. Compared with values before treatment, FIF50 and forced expiratory volume in 1 sec (FEV1) did not change significantly. The dose of methacholine causing a 20% fall in FEV1 (PD20FEV1) and PD25FIF50 values were significantly increased from 2.40,±,1.39 to 4.22,±,1.13 mg /mL (P,<,0.001) and from 1.03,±,1.75 to 8.71,±,1.21 mg /mL (P,<,0.0001), respectively. We conclude that measurements of EAHR and BHR are the most important ways to evaluate children with asthma-like symptoms, including chronic persistent cough when chest X-rays and pulmonary function tests remain within normal limits. Therefore, empirical treatment is not necessary when these investigations are available. Our results suggest that specific treatment of inflammation in the upper airways reversed persistant cough, and may play an important role in modulating lower airways responsiveness in patients with concomitant BHR. Pediatr Pulmonol. 2002; 34:172,180. © 2002 Wiley-Liss, Inc. [source] Association of tobacco smoke exposure and respiratory syncitial virus infection with airways reactivity in early childhoodPEDIATRIC PULMONOLOGY, Issue 6 2001Alan Adler MD Abstract Exposure to infectious agents and environmental tobacco smoke are thought to induce bronchial hyperresponsiveness (BHR). This study was undertaken to determine the effects of passive exposure to tobacco smoke and respiratory syncitial virus (RSV) lower respiratory infection (LRI) during infancy on the occurrence of BHR in the first 2 years of life. Eighty-six cases of documented RSV (mean age, 188 days) and 78 controls (mean age, 162 days) were enrolled from the clinic and in-patient service of a single hospital. None had a history of prior LRI. Subjects were studied at 6-month intervals up to 19 months of age with a standardized respiratory illness and parental smoking questionnaire, partial expiratory flow-volume curves by the "hug" (rapid thoracic compression) technique, and methacholine challenge. Exposure to maternal and paternal cigarette smoking, maternal history of asthma, and mold exposure were associated with decreased levels of length-corrected maximal flow at functional residual capacity (V,maxFRC). RSV-LRI was not related to V,maxFRC. After adjustment of V,maxFRC for these factors, V,maxFRC was a significantly and positively correlated with a methacholine concentration provoking a 40% fall in V,maxFRC (PC40) and negatively correlated with dose-response slope. After adjustment for V,maxFRC, there were no independent effects of tobacco smoke exposure or RSV-LRI on methacholine responses. These data do not support a role for RSV as a risk factor for airways reactivity in childhood and indicate that exposure to tobacco smoke affects airways reactivity through its effects on airways. Pediatr Pulmonol. 2001; 32:418,427. © 2001 Wiley-Liss, Inc. [source] Inflammation and remodeling in the adult and child with asthmaPEDIATRIC PULMONOLOGY, Issue S21 2001Peter Jeffery MSc Abstract Inflammation and remodeling are characteristic features of the conducting airways in asthma, but the relationships between inflammation, inappropriate remodeling, bronchial hyperresponsiveness, and reduced pulmonary function are still unclear. In both adults and children with asthma, there are structural changes of the conducting airways that include injury and loss of the surface epithelium, thickening of the reticular basement membrane, increases of underlying collagen, blood vessels, and airway smooth muscle, and plugging of the airways by exudate. Bronchial biopsies obtained from persons with mild stable asthma already demonstrate the presence of inflammation. Many of the inflammatory and structural changes begin early in childhood. Whereas corticosteroids markedly reduce many aspects of inflammation, it is not known whether and how they affect the changes associated with airway wall remodeling. Leukotriene receptor antagonists appear to be antiinflammatory and able to reduce the proliferation of bronchial smooth muscle. Pediatr Pulmonol. 2001; Supplement 21:3,16. © 2001 Wiley-Liss, Inc. [source] Relationship between bronchial hyperresponsiveness and development of asthma in children with chronic coughPEDIATRIC PULMONOLOGY, Issue 6 2001Hideko Nishimura MD Abstract To evaluate the relationship between bronchial hyperresponsiveness (BHR) and the development of asthma in children with chronic cough, we performed methacholine inhalation challenges and transcutaneous oxygen pressure (tcPO2) measurements in 92 children with chronic cough aged from 1,13 years (55 boys and 37 girls; mean, 5.3 years) and followed them for ,,,10 years. Forty-four age-matched children with asthma (24 males and 20 females; mean, 6.5 years) and 44 age-matched children without cough or asthma served as controls (18 males and 26 females; mean, 4.6 years). Consecutive doubling doses of methacholine were inhaled until a 10% decrease in tcPO2 from baseline was observed. The cumulative dose of methacholine at the inflection point of the tcPO2 record (Dmin-PO2) was considered to represent hyperresponsiveness to inhaled methacholine. After 10 years or more of follow-up, 60 of the 92 subjects with cough answered our questionnaire, and 27/60 had been diagnosed with asthma. There was a statistical difference in Dmin-PO2 between the children who presented with chronic cough originally and who developed asthma (asthma-developed group) and those who did not develop asthma (asthma-free group). There was no difference in the value of Dmin-PO2 between the asthma-developed group and the asthma group, or between the asthma-free group and the age-matched control group. Among the children with chronic cough, there was no difference in Dmin-PO2 between girls and boys, either in the asthma-developed group or in the asthma-group. We conclude that 45% of the children with a chronic cough in early life developed asthma, and that BHR in children with chronic cough during the childhood period is a strong risk factor for the development of asthma. Pediatr Pulmonol. 2001; 31:412,418. © 2001 Wiley-Liss, Inc. [source] Inhalation incidents and respiratory health: results from the European Community respiratory health surveyAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 1 2009Maria C. Mirabelli MPH Abstract Background Inhalation incidents are an important cause of acute respiratory symptoms, but little is known about how these incidents affect chronic respiratory health. Methods We assessed reported inhalation incidents among 3,763 European Community Respiratory Health Survey (ECRHS) participants with and without cough, phlegm, asthma, wheezing or bronchial hyperresponsiveness. We then examined whether inhalation incidents during the 9-year ECRHS follow-up period were associated with a new onset of any of these respiratory outcomes among 2,809 participants who were free of all five outcomes at the time of the baseline ECRHS survey. Results Inhalation incidents were reported by 5% of participants, with higher percentages reported among individuals with asthma-related outcomes at the time of the baseline survey. Among participants without symptoms at baseline, our analyses generated non-statistically significant elevated estimates of the risk of cough, phlegm, asthma and wheezing and a non-statistically significant inverse estimate of the risk of bronchial hyperresponsiveness among participants who reported an inhalation incident compared to those without such an event reported. Discussion Our findings provide limited evidence of an association between inhalation incidents and asthma-related symptoms. These data could be affected by differences in the reporting of inhalation incidents according to symptom status at the time of the baseline survey; they should thus be interpreted with caution. Am. J. Ind. Med. 52:17,24, 2009. © 2008 Wiley-Liss, Inc. [source] Excess of symptoms among radiographers,AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 2 2003Helen Dimich-Ward PhD Abstract Background The prevalence and occupational determinants of miscellaneous symptoms referred to as "Darkroom disease" was compared between radiographers and physiotherapists working in British Columbia, Canada. Methods The participation rate for the mailout questionnaire survey was 66.1%. A small subset underwent spirometry and methacholine challenge testing. Results Radiographers had a higher prevalence of most symptoms, with an extreme odds ratio of 11.4 for chemical/metallic taste. The percentage of radiographers with non-specific bronchial hyperresponsiveness (NSBHR) was 3 times higher than that of physiotherapists, although the comparison was not statistically significant. Reporting inadequate ventilation, frequently detecting the odor of X-ray processing chemicals and cleaning up spills within the past 12 months were highly associated with most of the symptoms. Conclusions Our results suggest that differences in the prevalence of symptoms represent a complex process, both in exposure and response to the many constituents found in radiographic processing chemicals. Objective testing of health outcomes and more refined exposure measurements are recommended to further investigate occupational health problems of radiographers. Am. J. Ind. Med. 43: 132,141, 2003. © 2003 Wiley-Liss, Inc. [source] Resistance and reactance in oscillation lung function reflect basal lung function and bronchial hyperresponsiveness respectivelyRESPIROLOGY, Issue 7 2009Hyeong Yoon KIM ABSTRACT Background and objective: Currently there are few data available regarding the use of impulse oscillometry parameters to assess airflow obstruction during standardized methacholine challenge testing. Methods: Methacholine challenge tests were performed using impulse oscillometry and conventional spirometry in 64 healthy and 39 asthmatic children, in order to determine airway resistance (R) and reactance (X) at frequencies of 5,35 Hz, as well as FEV1. Results: Baseline R and X were significantly different between the healthy and asthmatic children, with the most discriminating parameter being resistance at 5 Hz (R5). In asthmatic children BHR was well demonstrated by FEV1, X5 and X10, but not by R5. However, when the actual R5 values obtained in this study were compared with the predicted values, there appeared to be differences in the lung function measures that corresponded to varying methacholine concentrations. In addition, the PC20_FEV1 and PC70_X5 were significantly more sensitive than other parameters for methacholine challenge testing. Conclusions: Measuring resistance at 5 Hz using impulse oscillometry facilitates significant differentiation of baseline lung function between asthmatic and healthy children. Additionally, X may be a suitable replacement for PC20 in methacholine challenge testing. [source] Inhaled corticosteroid for persistent cough following upper respiratory tract infectionRESPIROLOGY, Issue 4 2005Prapaporn PORNSURIYASAK Objective: The aim of this study was to determine the clinical effect of inhaled corticosteroid treatment for persistent cough, post upper respiratory tract infection (URTI) in previously healthy individuals, and on bronchial hyperresponsiveness (BHR). Methodology: This was a prospective, randomized, double-blinded, placebo-controlled study conducted at a university hospital. A total of 30 non-asthmatic, non-smoking patients who were >15 years old and who had persistent post-URTI cough for >3 weeks were assessed by a physical examination, CXR and spirometry, and were allocated to receive inhaled budesonide (400 µg/puff, twice daily) or placebo for 4 weeks. If a patient suffered from sinusitis, it was a requirement that it had been well treated. A symptom score (frequency of cough, frequency of coughing bouts, symptoms associated with cough, night-time cough, frequency of taking medications to relieve cough, and number of medications) was recorded at entry, and after 2 and 4 weeks of treatment. A methacholine challenge test was performed at entry and after 4 weeks of treatment. Results: The mean symptom scores for the treatment group (9.4) and the placebo group (9.8) at baseline were not significantly different (P = 0.79), and no differences were found between the groups after week 2 and week 4 of treatment (3.93 and 4.27 vs 2.26 and 2.66, P = 0.29). The mean change in symptom scores from baseline to week 2 and to week 4 of treatment were also not different between groups (5.93 and 5.6 vs 7.00 and 7.58, P = 0.23). No difference between groups was found in the mean changes in FEV1, FVC, and FEF25,75% after 4 weeks of treatment. A positive bronchial provocation test occurred in three patients (10%) but these were borderline. Conclusion: Inhaled corticosteroid is ineffective in treating persistent post-URTI cough in previously healthy individuals. [source] Sputum eosinophilia and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapyRESPIROLOGY, Issue 2 2003Keisaku FUJIMOTO Objective: We aimed to examine airway inflammation and bronchial responsiveness in patients with chronic non-productive cough responsive to anti-asthma therapy. Methodology: Bronchial responsiveness to methacholine as well as the number of inflammatory cells and concentration of eosinophil cationic protein (ECP) in induced sputum were measured in 42 patients with chronic non-productive cough of unknown origin. Their response to bronchodilator, antiallergic and inhaled or oral glucocorticoid therapy was subsequently assessed. Results: Complete remission of coughing was attained with anti-asthma therapies in 34 patients (responder group), while eight patients did not respond (non-responder group). Twenty patients in the responder group and three in the non-responder group showed bronchial hyperresponsiveness (BHR). The number of eosinophils and ECP levels in the sputum from responders with BHR were significantly increased when compared with those from non-responders and healthy subjects. These sputum measures were also significantly increased in responders without BHR when compared with healthy subjects. However, there were no significant differences in these inflammatory markers between the responders with and without BHR. The neutrophil numbers in the sputum from non-responders and responders both with and without BHR were also significantly higher than in control subjects, but there were no significant differences. Conclusions: These findings suggest that patients with chronic non-productive cough responsive to anti-asthma therapy characteristically have eosinophilic airway inflammation, which may play an important role in the development of chronic cough. Furthermore, the evaluation of not only bronchial responsiveness but also airway inflammation by examination of induced sputum may be useful for diagnosis and deciding on therapeutic strategies. [source] Monitoring asthma therapy using indirect bronchial provocation tests,THE CLINICAL RESPIRATORY JOURNAL, Issue 1 2007John D. Brannan Abstract Objectives:, Bronchial provocation tests that assess airway hyperresponsiveness (AHR) are known to be useful in assisting the diagnosis of asthma and in monitoring inhaled corticosteroid therapy. We reviewed the use of bronchial provocation tests that use stimuli that act indirectly for monitoring the benefits of inhaled corticosteroids. Data Source:, Published clinical trials investigating the effect of inhaled corticosteroids on bronchial hyperresponsiveness in persons with asthma were used for this review. Study Selection:, Studies using indirect stimuli to provoke airway narrowing such as exercise, eucapnic voluntary hyperventilation, cold air hyperventilation, hypertonic saline, mannitol, or adenosine monophosphate (AMP) to assess the effect of inhaled corticosteroids were selected. Results:, Stimuli acting indirectly result in the release of a variety of bronchoconstricting mediators such as leukotrienes, prostaglandins, and histamine, from cells such as mast cells and eosinophils. A positive response to indirect stimuli is suggestive of active inflammation and AHR that is consistent with a diagnosis of asthma. Persons with a positive response to indirect stimuli benefit from daily treatment with inhaled corticosteroids. Symptoms and lung function are not useful to predict the long-term success of inhaled corticosteroid dose as they usually resolve rapidly, and well before inflammation and AHR has resolved. Following treatment, AHR to indirect stimuli is attenuated. Further, during long-term treatment, asthmatics can become as non-responsive as non-asthmatic healthy persons, suggesting that asthma is not active. Conclusions:, Non-responsiveness to indirect bronchial provocation tests following inhaled corticosteroids occurs weeks to months following the resolution of symptoms and lung function. Non-responsiveness to indirect stimuli may provide a goal for adequate therapy with inhaled corticosteroids. Please cite this paper as: Brannan JD, Koskela H and Anderson SD. Monitoring asthma therapy using indirect bronchial provocation tests. The Clinical Respiratory Journal 2007;1:3,15. [source] Identifying problematic severe asthma in the individual child , does lung function matter?,ACTA PAEDIATRICA, Issue 3 2010AM Lang Abstract Aim:, Measures of lung function (usually FEV1 <80% predicted) are used to classify asthma severity in both adults and children, despite evidence that lung function impairment is less pronounced in the paediatric asthma population. The present study assesses the relevance of lung function measurements as discriminators of severe childhood asthma. Methods:, Fifty-one school-aged children with problematic severe asthma, 37 mild-to-moderate asthmatics and 29 healthy controls underwent a comprehensive clinical work-up. Problematic severe asthma was defined in patients exhibiting poor asthma control despite high-dose inhaled corticosteroid treatment and at least one other asthma controller drug. Mild-to-moderate asthmatic children used low-dose inhaled steroids and reported minimal asthma symptoms. Results:, Baseline FEV1 values were significantly reduced in children with problematic severe asthma, yet FEV1 <80% predicted showed a low sensitivity (41%) for discriminating severe vs. mild-to-moderate asthma. Receiver-operated characteristic analysis estimated the optimal cut-off of FEV1 to be 90% predicted in this population (sensitivity 61%, specificity 83%). Baseline FEV1/FVC and FEF25,75 values were not superior to FEV1 in discriminating problematic severe asthma, and neither exhaled nitric oxide levels nor bronchial hyperresponsiveness differentiated between the two asthmatic study populations. Conclusion:, Spirometric measurements are insensitive discriminators of problematic severe asthma in childhood. [source] Association between asthma control and bronchial hyperresponsiveness and airways inflammation: a cross-sectional study in daily practiceCLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2009V. Quaedvlieg Summary Background The primary end-point in the management of asthma is to obtain optimal control. The aim of this study was to assess the relationships between the markers of airway inflammation (sputum eosinophilia and exhaled nitric oxide), bronchial hyperresponsiveness (BHR) and asthma control. Methods One hundred and thirty-four patients were recruited from our asthma clinic between January 2004 and September 2005 [mean age: 42 years, mean forced expiratory volume in 1 s (FEV1): 86% predicted]. Eighty-six of them were treated by inhaled corticosteroids, 99 were atopic and 23 were current smokers. They all underwent detailed investigations including fractional-exhaled nitric oxide (FENO) measurement, sputum induction and methacholine challenge when FEV1 was >70% predicted, and filled in a validated asthma control questionnaire (ACQ6 Juniper). Results When dividing patients into the three groups according to their level of asthma control determined by ACQ [well-controlled asthma (ACQ score 0.75), borderline (0.75 Relationship between oxidative stress-related biomarkers and antioxidant status with asthma and atopy in young adults: a population-based studyCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2009V. García-Larsen Summary Background and aim Enhanced oxidative stress has been described in adults who suffer from symptoms of asthma and poor lung function. This study assessed the relation between markers of oxidative stress and antioxidant status and lung function, symptoms of asthma, atopy and bronchial hyperresponsiveness (BHR) in young adults. Methods A sub-sample of 589 individuals aged 22,28 years, selected from a total of 1232 included in a survey assessing early and current risk factors for chronic diseases, participated in the study. Participants were from an agricultural area of Chile, responded to a Spanish version of the European Community Respiratory Health Survey questionnaire, were skin tested to eight allergens, and challenged with methacholine to assess BHR. Five hundred and eighty-five individuals had measures of plasma biomarkers ferric reducing ability of plasma, uric acid, protein carbonyls and 564 had 8-iso-prostaglandin F2, (8-iso-PGF2,) assessed. Results All participants had detectable plasma 8-iso-PGF2, and carbonyl levels. There was no indication for an association between markers of antioxidant status or oxidative stress with any of the outcomes studied. Conclusion The levels of oxidative stress-related biomarkers and antioxidant status in plasma may not be related to asthma in the general population in the absence of more severe symptoms or exacerbations. [source] Immunoglobulin E antibodies enhance pulmonary inflammation induced by inhalation of a chemical haptenCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2009C. B. Mathias Summary Background Occupational exposure to chemicals is an important cause of asthma. Recent studies indicate that IgE antibodies enhance sensitization to chemicals in the skin. Objective We investigated whether IgE might similarly promote the development of airway inflammation following inhalation of a contact sensitizer. Methods A model of chemical-induced asthma is described in which introduction of the low-molecular-weight compound, trinitrobenzene sulphonic acid (TNBS), via the respiratory tract was used for both sensitization and challenge. The role of IgE antibodies in the immune response to inhaled TNBS in this model was assessed by comparing the responses of wild-type (WT) and IgE-deficient (IgE,/,) mice on the BALB/c background. Reconstitution of circulating IgE levels by intravenous injection of IgE antibodies into IgE,/, mice before sensitization was performed to confirm the role of IgE in any differences observed between the responses of WT and IgE,/, mice. Results Intranasal challenge of TNBS-sensitized (but not sham-sensitized control mice) induced intense pulmonary inflammation. Macrophages, eosinophils and lymphocytes, including T, B, natural killer and natural killer T cells, were recruited to the airway and the animals displayed bronchial hyperresponsiveness (BHR) to methacholine. Serum levels of murine mast cell protease-1 (mMCP-1) were elevated suggesting mast cell activation. In contrast, the development of airway inflammation, recruitment of lymphocytes, induction of BHR and production of mMCP-1 were all significantly attenuated in IgE-deficient mice. Reconstitution of IgE,/, mice with IgE (of unrelated antigen specificity) before sensitization partially restored these features of asthma. Conclusion Our data indicate that IgE antibodies non-specifically enhance the development of airway inflammation induced by exposure to chemical antigens. [source] Association of polymorphisms in CASP10 and CASP8 with FEV1/FVC and bronchial hyperresponsiveness in ethnically diverse asthmaticsCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2008Alicia K. Smith Summary Background Several chromosomal regions have been identified using family-based linkage analysis to contain genes contributing to the development of asthma and allergic disorders. One of these regions, chromosome 2q32-q33, contains a gene cluster containing CFLAR, CASP10 and CASP8. These genes regulate the extrinsic apoptosis pathway utilized by several types of immune and structural cells that have been implicated in the pathogenesis of asthma. Objective To assess the role of genetic variation in CFLAR, CASP10 and CASP8 in asthma and related phenotypes in individuals of diverse ethnic backgrounds. Methods We tested 26 single nucleotide polymorphisms (SNPs) in the CFLAR, CASP10 and CASP8 gene cluster for association with asthma and related phenotypes in African-American, non-Hispanic whites, and Hispanic case,control populations (cases, N=517, controls, N=644). Results Five CASP10 SNPS were associated with forced expiratory volume in 1 s (FEV1)/forced expiration volume capacity (FVC) in the African-American subjects with asthma (P=0.0009,0.047). Nine SNPs, seven in CASP10 and two in CASP8, were also associated with the degree of bronchial hyperresponsiveness (BHR) (as determined by PC20) in race-specific analysis, predominately in the Non-Hispanic white cases. Two SNPs, rs6750157 in CASP10 and rs1045485 in CASP8 were modestly associated with asthma in the African-American (P=0.025) and Hispanic (P=0.033) populations, respectively. Conclusion These data suggest a role for CASP10 as a potential modifier of the asthma phenotype, specifically with measures of airway obstruction and BHR. [source] Impact of specific sensitization on asthma and rhinitis in young Brazilian and Chilean adultsCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2008R. J. Rona Summary Background The pattern of associations and the attributable fractions (AF) of atopic conditions due to specific sensitizations vary between countries. Objective To assess the level of associations and AF between sensitization to five allergens and atopic conditions in two settings. Methods We studied 2063 Brazilians and 1231 Chileans of both sexes using representative samples selected at birth in the 1970s. Information on asthma and rhinitis was based on the European Community Respiratory Health Survey questionnaire. We assessed bronchial hyperresponsiveness (BHR) to methacholine and sensitization to Dermatophagoides pteronyssinus, cat, dog, grass blend and Alternaria alternata. Results The prevalence of sensitization to one or more allergens was 50% in Brazilians and 22% in Chileans. The level of associations varied according to the outcome used. Strong associations between sensitization and asthma, defined as wheeze or awakening with breathlessness at night and positive BHR, were found for each of the five allergens in Chileans [varying from odds ratio (OR) 3.24, 95% confidence interval (CI) 1.47, 7.15 for D. pteronyssinus to 8.44, 95% CI 3.82, 18.66 for cat], whereas the level of associations was restricted to D. pteronyssinus, cat and dog in Brazilians and was somewhat weaker (highest OR 3.90, 95% CI 2.80,5.44). The AF of sensitization on asthma was 54% in Brazil and 44% in Chile. D. pteronyssinus and cat made an independent contribution to asthma in the two samples. The patterns of associations between sensitization and rhino-conjunctivitis were similar to those for asthma. Conclusion The associations between sensitization, and asthma and rhinitis were high in Chile and moderately high in Brazil, but the AF were higher in Brazil, reflecting a higher prevalence of sensitization. In Brazil, dust mite had the greatest impact on atopic conditions while in Chile several allergens had an impact. Sensitization is as serious a problem in Chile and Brazil as in developed countries. [source] Roles of P2X receptors and Ca2+ sensitization in extracellular adenosine triphosphate-induced hyperresponsiveness in airway smooth muscleCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2007T. Oguma Summary Background The release of adenosine triphosphate (ATP) from the airway epithelial cells during the inflammatory process is considered to play an important role in the pathophysiology of asthma and chronic obstructive pulmonary disease. Objective This study was designed to determine whether extracellular ATP is involved in the bronchial hyperresponsiveness as an interaction between epithelium and smooth muscle in the airways. Methods We examined the contractile response to methacholine (MCh) before and after exposure to low concentrations (10 ,m) of ATP in isolated, epithelium-denuded guinea-pig tracheal smooth muscle by measuring isometric tension. Intracellular Ca2+ concentrations ([Ca2+]i) were assessed by fluorescent intensities of fura-2. Results MCh-induced contractile force was increased with no change in [Ca2+]i after exposure to 10 ,m ATP for 15 min. The ability of ATP to enhance the MCh-induced contraction was markedly attenuated by suramin, a non-selective P2 receptor inhibitor. Pre-incubation with ATP,S, a non-hydrolysable analogue of ATP and ,,,-meATP, a P2X agonist, also enhanced the MCh-induced contraction. In contrast, uracil triphosphate, a P2Y agonist, did not affect the MCh-induced contraction. Y-27632, a Rho-kinase inhibitor, suppressed the ability of ATP to enhance the MCh-induced contraction. Moreover, PP1 and PP2, Src tyrosin kinase inhibitors, suppressed the enhancement of MCh-induced contraction by ATP. Conclusion Pre-treatment with ATP induces hyperresponsiveness to MCh mediated by Ca2+ sensitization via the P2X receptor in airway smooth muscle. The present findings suggest the possible involvement of both the Rho-kinase and Src pathways in the intracellular mechanism of this phenomenon. [source] Allergen-induced airway inflammation and bronchial responsiveness in interleukin-5 receptor , chain-deficient miceCLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2000Tanaka Objective The role of IL-5 receptor , chain (IL-5R,) in the onset of bronchial hyperresponsiveness (BHR) to acetylcholine was investigated by testing IL-5R, knockout (IL-5R, KO) mice. Methods Mice were immunized with antigen at intervals of 12 days. Starting 10 days after the secondary immunization, mice were exposed to antigen three times every fourth day. Twenty-four hours after the last antigen challenge, bronchial responsiveness to acetylcholine was measured and bronchoalveolar lavage was carried out. Results Twenty-four hours after the last antigen inhalation, total and differential cells counts of bronchoalveolar lavage revealed a significant increase in eosinophils and lymphocytes in ovalbumin-exposed wild-type mice. In IL-5R, KO mice, there was little increase of eosinophils in bronchoalveolar lavage fluid (BALF). The production of IL-5 in BALF increased in both mice after repeated antigen challenge, and there was no significant difference between wild-type and IL-5R, KO mice. Similar to the BAL study, histological sections of lung tissue from ovalbumin-exposed wild-type mice exhibited airway eosinophilic inflammation, which was attenuated by the deficiency of IL-5R, chain. There was no significant difference in serum antigen-specific IgE levels between wild-type and IL-5R, KO mice after immunization nor antigen inhalation. Repeated antigen provocation caused BHR to acetylcholine in wild-type mice. In contrast, no BHR was observed in IL-5R, KO mice after repeated inhalation of antigen. Conclusion These findings indicate that IL-5R, plays an important role in the development of antigen-induced airway eosinophilia and BHR in mice. [source] Allergic rhinitis and asthma: epidemiological evidence for the linkCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 1 2003C. H. Katelaris Summary For years, a clinical relationship between allergic rhinoconjunctivitis (AR/C) and asthma has been observed. Recently, evidence supporting this link has been published. An important body of evidence for a real link between the two conditions has come from epidemiological studies. An increasing prevalence of both conditions is noted in the developed and developing countries. A number of studies have documented the co-existence of AR/C and asthma, with one group reporting up to 80% of patients with asthma having AR/C. Increased bronchial hyperresponsiveness, one of the characteristic findings in asthma, is also demonstrated in those with AR/C even in the absence of clinical asthma. There are a number of common factors linking the two conditions. Atopy is a risk factor for the development of both asthma and AR/C, as is the finding of positive skin tests to common aeroallergens. There is also a well documented temporal relationship between the two conditions, with AR/C beginning soon before or simultaneously with asthma , an association noted in a number of studies examining large groups of subjects . Finally, there are a few studies that demonstrate treatment of one condition leading to an effect on the other , this has been particularly noted with the improvement in asthma control once AR/C has been adequately managed. Given the growing evidence of common factors between the two conditions and the frequent finding that they co-exist in the same patient, management strategies must include treatment of both the upper and the lower airway rather than focusing only on the predominant complaint. [source]
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