Does bronchial hyperresponsiveness predict a diagnosis of cough variant asthma in adults with chronic cough: a cohort study.
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SUBMITTER: Rybka-Fraczek A
PROVIDER: S-EPMC8461979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMany patients with cough variant asthma (CVA) are underdiagnosed and undertreated due to the atypical symptoms, low diagnostic sensitivity of bronchodilator response (BDR), and limited application of bronchial challenge test.ObjectiveTo investigate whether airway reversibility in BDR can predict CVA diagnosis in patients with chronic cough and negative BDR.MethodsThis open-label, prospective cohort study included patients with chronic cough, nearly normal chest CT scan, and negative BDR results. Inhaled corticosteroids and long-acting β2 agonists were given for 4 weeks. The confirmed diagnosis of CVA was defined as improved symptoms and an increase of forced expiratory volume in 1 s (FEV1) by >12% and >200 mL after 4 weeks of treatment.ResultsOf 155 patients recruited, 140 completed the study. Patients in the CVA positive diagnosis group had greater absolute (Δ) and percent (Δ%) improvements in FEV1 and forced expiratory flows (FEFs), and higher fractional exhaled nitric oxide (FENO) than in the CVA negative diagnosis group. The area under the receiver operating characteristic curves (AUCs) of ΔFEV1%, FEF25-75%pred (percentage of predicted forced expiratory flow at 25% to 75%) and FENO for CVA positive diagnosis was 0.825, 0.714, and 0.637, with cutoff values of 5.90%, 61.99% and 41.50 ppb, respectively. A joint model of ΔFEV1% combined with FEF25-75%pred or FENO increased the AUC to 0.848 and 0.847, respectively.ConclusionΔFEV1% in BDR can predict a CVA diagnosis and response to anti-asthma treatment in patients with chronic cough and negative BDR.Clinical trial registration[http://www.chictr.org.cn/index.aspx], identifier [ChiCTR2000029065].
| S-EPMC9780531 | biostudies-literature
Project description:BackgroundThe AtyPical Asthma in China (APAC) cohort is a multi-center prospective, observational cohort set-up to investigate the clinical, pathophysiological features, prognosis, and mechanisms of cough variant asthma (CVA).ObjectivesTo present the characteristics of newly physician-diagnosed adults with CVA (n = 328) compared to mild-moderate classic asthma (CA, n = 206).Methods and main resultsCVA subjects showed a higher proportion of female (67.1 vs. 55.3%, P = 0.0084), abnormal laryngopharyngeal sensations (71 vs. 51%, p < 0.0001) than CA, but presented with near normal spirometry and higher methacholine PD20-FEV1 values [4.2 (1, 8.6) vs. 0.8 (0.4, 4.7), P < 0.0001]. Lower fractional exhaled nitric oxide (FENO) levels [38.5 (19.8, 72.5) vs. 53. (28.5, 92.2), P = 0.0019], blood eosinophil counts [0.2 (0.1, 0.4) vs. 0.3 (0.2, 0.5), P = 0.0014], and sputum eosinophils [2.3 (0.3, 8.0) vs. 12.2 (2, 34.5), p < 0.0001] were found in CVA. Despite lower total serum IgE levels in CVA, there was similar proportion of atopy in both groups. The prevalence of cough in CA was 86.4%, while CVA reported more severe cough on Visual Analog Scale, Cough Evaluation Test, and Leicester Cough Questionnaire, similar anxiety and depression scores but better asthma control scores as reflected by Asthma Control Test compared to CA. No correlation was found between cough assessment outcomes and sputum eosinophil count, blood eosinophil count, FENO, spirometry variables, or PD20-FEV1.ConclusionCough variant asthma is distinctive from classic asthma in regard to clinical features, lung function, and airway inflammation. Quality of life is badly impaired as well in spite of better asthma control scores.
| S-EPMC8814600 | biostudies-literature
Project description:BackgroundImprovement in lung function after macrolide antibiotic therapy has been attributed to reduction in bronchial infection by specific bacteria. However, the airway might be populated by a more diverse microbiota, and clinical features of asthma might be associated with characteristics of the airway microbiota present.ObjectiveWe sought to determine whether relationships exist between the composition of the airway bacterial microbiota and clinical features of asthma using culture-independent tools capable of detecting the presence and relative abundance of most known bacteria.MethodsIn this pilot study bronchial epithelial brushings were collected from 65 adults with suboptimally controlled asthma participating in a multicenter study of the effects of clarithromycin on asthma control and 10 healthy control subjects. A combination of high-density 16S ribosomal RNA microarray and parallel clone library-sequencing analysis was used to profile the microbiota and examine relationships with clinical measurements.ResultsCompared with control subjects, 16S ribosomal RNA amplicon concentrations (a proxy for bacterial burden) and bacterial diversity were significantly higher among asthmatic patients. In multivariate analyses airway microbiota composition and diversity were significantly correlated with bronchial hyperresponsiveness. Specifically, the relative abundance of particular phylotypes, including members of the Comamonadaceae, Sphingomonadaceae, Oxalobacteraceae, and other bacterial families were highly correlated with the degree of bronchial hyperresponsiveness.ConclusionThe composition of bronchial airway microbiota is associated with the degree of bronchial hyperresponsiveness among patients with suboptimally controlled asthma. These findings support the need for further functional studies to examine the potential contribution of members of the airway microbiota in asthma pathogenesis.
| S-EPMC3037020 | biostudies-literature
Project description:RationaleSecreted phospholipase A(2) enzymes (sPLA(2)s) play key regulatory roles in the biosynthesis of eicosanoids, such as the cysteinyl leukotrienes, but the role of these enzymes in the pathogenesis of asthma is not known.ObjectivesTo establish if sPLA(2)s are overexpressed in the airways of patients with asthma, and to determine if these enzymes may play a role in the generation of eicosanoids in exercise-induced bronchoconstriction.MethodsInduced sputum samples were obtained from subjects with asthma with exercise-induced bronchoconstriction and nonasthmatic control subjects at baseline, and on a separate day 30 minutes after exercise challenge. The expression of the PLA(2)s in induced sputum cells and supernatant was determined by quantitative polymerase chain reaction, immunocytochemistry, and Western blot.Measurements and main resultsThe sPLA(2)s expressed at the highest levels in airway cells of subjects with asthma were groups X and XIIA. Group X sPLA(2) (sPLA(2)-X) was differentially overexpressed in asthma and localized to airway epithelial cells and bronchial macrophages. The gene expression, immunostaining in airway epithelial cells and bronchial macrophages, and the level of the extracellular sPLA(2)-X protein in the airways increased in response to exercise challenge in the asthma group, whereas the levels were lower and unchanged after challenge in nonasthmatic control subjects.ConclusionsIncreased expression of sPLA(2)-X may play a key role in the dysregulated eicosanoid synthesis in asthma.
| S-EPMC2176098 | biostudies-literature
Project description:BACKGROUND:The aim of this study was to establish whether non-atopic patients with cough variant asthma (CVA) have different pattern of response to direct bronchoconstrictors than non-atopic patients with classic asthma (CA). METHOD:A total of 170 patients of both sexes with stable CVA and CA were screened for the study and 153 were included. Patients with proven atopy were not included and 17 patients with worsening of their condition or with verified bronchial obstruction during screening were excluded. All included patients performed spirometry and underwent a bronchial challenge with histamine according to long-standing protocol in our laboratory. RESULTS:Significantly higher frequency of bronchial hyper-responsiveness (BHR) was found in patients with CA than in patients with CVA (63.9% vs. 44.9%, respectively; p < 0.05). Sensitivity was significantly lower in patients with CVA (p < 0.05), while no significant difference was found in maximal response and responsiveness. Only patients with positive challenge tests were included in the analysis. CONCLUSION:Adult non-atopic patients with CVA and CA have a pattern of response to non-specific bronchial stimuli similar to atopic patients with same conditions, with the exception of similar maximal response, which may reflect the efficacy of previous treatment. We believe that further studies are needed to clarify the mechanisms involved in airway response to non-specific stimuli in CVA and CA, especially in non-atopic patients. Further studies should also clarify whether this response pattern has any implications on clinical presentation or on treatment options.
| S-EPMC6069128 | biostudies-literature
Project description:BackgroundBronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control.MethodsMethacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double-blind, placebo-controlled food challenge and 80 control children without food allergy. Of the 89 food-allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6-12 months of OIT.ResultsMethacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut-allergic versus the control children (1009 μg, 1104 μg, and 2068 μg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome.ConclusionBHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.
| S-EPMC9549178 | biostudies-literature
Project description:BACKGROUND:The management of asthma has changed since the introduction of budesonide/formoterol (Symbicort®) as both maintenance and reliever therapy (SMART). SMART and its effects on bronchial hyperresponsiveness (BHR) have not been studied in primary care. AIMS:To compare the effects of SMART and guideline-driven usual care (UC) on BHR and clinical asthma severity in primary care practice. METHODS:Patients with mild-to-moderate stable asthma were randomised to receive SMART treatment (n=54) (budesonide/formoterol 80/4.5 ?g Turbuhaler®, two puffs once daily and extra inhalations as needed) or UC treatment (n=48) for 12 months. Diary data, Asthma Control Questionnaire scores, forced expiratory volume in 1 second (FEV1), and peak expiratory flow (PEF) measurements were collected during run-in and after 1, 3, 6, and 12 months of treatment. BHR, measured as the dose of histamine provoking a fall in FEV1 of 20% (PD20-histamine), was determined at randomisation and after 12 months. RESULTS:One hundred and two patients with asthma participated in the study. The change in PD20-histamine during the study was not significantly different between the SMART and UC groups (p=0.26). The mean inhaled corticosteroid (ICS) dose was 326 ?g beclomethasone dipropionate (BDP) equivalents/day (95% CI 254 to 399) with SMART, which was significantly lower (p<0.0001) than the mean ICS dose with UC treatment (798 ?g BDP equivalents/day (95% CI 721 to 875). Morning and evening PEF values increased significantly with SMART treatment compared with UC; FEV1, symptoms and asthma control did not differ. CONCLUSIONS:Despite a 59% lower dose of ICS, BHR and other clinical outcomes remained stable during SMART treatment while PEF values improved.
| S-EPMC6548307 | biostudies-literature
Project description:IntroductionOver the past 50 years, the prevalence of allergic respiratory diseases has been increasing. The Hygiene hypothesis explains this progression by the decrease in the bio-diversity of early microbial exposure. This study aims to evaluate the effect of early-life farm exposure on airway hyperresponsiveness and cough hypersensitivity in an allergic airway inflammation rabbit model.MethodA specific environment was applied to pregnant rabbits and their offspring until six weeks after birth. Rabbits were housed in a pathogen-free zone for the control group and a calf barn for the farm group. At the end of the specific environmental exposure, both groups were then housed in a conventional zone and then sensitized to ovalbumin. Ten days after sensitization, the rabbit pups received ovalbumin aerosols to provoke airway inflammation. Sensitization to ovalbumin was assessed by specific IgE assay. Cough sensitivity was assessed by mechanical stimulation of the trachea, and bronchial reactivity was assessed by methacholine challenge. The farm environment was characterized by endotoxin measurement.ResultsA total of 38 rabbit pups were included (18 in the farm group). Endotoxin levels in the farm environment varied from 30 to 1854 EU.m-3. There was no significant difference in specific IgE values to ovalbumin (p = 0.826) between the two groups. The mechanical threshold to elicit a cough did not differ between the two groups (p = 0.492). There was no difference in the number of cough (p = 0.270) or the intensity of ventilatory responses (p = 0.735). After adjusting for age and weight, there was no difference in respiratory resistance before and after methacholine challenge.ConclusionEarly exposure to the calf barn did not affect cough sensitivity or bronchial reactivity in ovalbumin-sensitized rabbits. These results suggest that not all farm environments protect against asthma and atopy. Continuous exposure to several sources of microbial diversity is probably needed.
| S-EPMC9882901 | biostudies-literature
Project description:BackgroundIt is unclear in which periods of life lung function deficits develop, and whether these are affected by risk factors such as asthma, bronchial hyper-responsiveness (BHR) and allergic comorbidity. The goal of this systematic review was to identify temporal associations of asthma, BHR and allergic comorbidity with large and small lung function development from birth until peak function in early adulthood.MethodsWe searched MEDLINE, EMBASE, Web of Science and CINAHL for papers published before 01.01.2020 on risk factors and lung function measurements of large and small airways. Studies were required to report lung function at any time point or interval from birth until peak lung function (age 21-26) and include at least one candidate risk factor.ResultsOf the 45 papers identified, 44 investigated cohorts and one was a clinical trial with follow-up. Asthma, wheezing, BHR and allergic sensitization early in life and to multiple allergens were associated with a lower lung function growth of large and small airways during early childhood compared with the control populations. Lung function development after childhood in subjects with asthma or persistent wheeze, although continuing to grow at a lower level, largely tracked parallel to non-affected individuals until peak function was attained.Clinical implications and future researchDeficits in lung function growth develop in early childhood, and children with asthma, BHR and early-life IgE (poly)sensitization are at risk. This period is possibly a critical window of opportunity to identify at-risk subjects and provide treatment aimed at preventing long-term sequelae of lung function.
| S-EPMC8453965 | biostudies-literature
Project description:These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.
| S-EPMC6942543 | biostudies-literature