Reversible Bronchoconstriction Research Articles

Therapeutic Potential of Vitamin D in Asthma Control

In 2019, according to WHO estimates, 262 million people were affected by asta, resulting in 455,000 deaths. Asthma, is a chronic inflammatory disease of the airways that causes reversible bronchoconstriction, making it difficult for patients to breathe. Exacerbations of the disease can be caused by a variety of factors but share similar symptoms such as wheezing, coughing, shortness of breath and chest tightness. Severe asthma exacerbations are defined as symptoms that do not respond to inhaled medications and improve only after oral or intravenous steroid administration. Asthma-related deaths often occur during exacerbations. Vitamin D, which is produced naturally in the body and found in some foods, is a steroid-derived vitamin. Adequate doses of this vitamin, administered through medication or supplements, can be used to maintain its proper levels in the organism. Vitamin D is essential for regulating calcium levels in the body and for bone remodeling. It also has immunomodulatory effects, affecting both innate and adaptive immunity. This partly explains its association with changes in the airway epithelium that occur as a result of inflammation in asthma. The study aims to summarize the current knowledge on the relationship of vitamin D with asthma symptom control. The present study is based on literature available in scientific databases from 2013-2016, such as PubMed, Corchane Library and Google Scholar, using the following keywords: "vitamin D" and "asthma." Vitamin D deficiency is prevalent in children and adults worldwide. A critical analysis of the literature reveals that the therapeutic administration of vitamin D has no apparent advantage in treating asthma, especially in children. Nevertheless, for adults with mild asthma, vitamin D supplementation shows promise for improved outcomes. However, there is a pressing need for large-scale clinical trials to determine the efficacy and safety of this therapeutic approach for both age groups.

Effect of VEGF Stimulation on CD11b Receptor on Peripheral Eosinophils in Asthmatics.

Asthma is a chronic, complex disease associated with heterogeneity in molecular pathways. Airway inflammation with different cell activation (e.g., eosinophils) and with hypersecretion of many cytokines (e.g., vascular endothelial growth factor-VEGF) might be relevant for asthma pathogenesis and responsible for airway hyperresponsiveness and remodeling. The aim of our study was to reveal the expression of activation marker CD11b on peripheral eosinophils unstimulated and after VEGF in vitro stimulation in asthmatics with different degrees of airway narrowing. The study population included a total of 118 adult subjects: 78 patients with asthma (among them 39 patients with irreversible bronchoconstriction and 39 patients with reversible bronchoconstriction according to the bronchodilation test) and 40 healthy participants as a control group. CD11b expression on peripheral blood eosinophils was detected in vitro using the flow cytometric method without exogenous stimulation (negative control), after N-formyl-methionine-leucyl-phenylalanine stimulation (fMLP; positive control) and after stimulation with VEGF in two concentrations (250 ng/mL and 500 ng/mL). CD11b marker was slightly presented on unstimulated eosinophils in asthmatics and the subgroup with irreversible airway narrowing (p = 0.06 and p = 0.07, respectively). Stimulation with VEGF enhanced the activity of peripheral eosinophils and induced CD11b expression in asthmatics in comparison with a healthy control (p < 0.05), but it was dependent neither on the concentration of VEGF nor on the degree of airways narrowing in patients with asthma. We present our findings to draw attention to the potential role of VEGF in the eosinophil priming and CD11b-mediated signaling in patients with asthma which is currently undervalued.

Airway remodeling heterogeneity in asthma and its relationship to disease outcomes.

Asthma affects an estimated 262 million people worldwide and caused over 461,000 deaths in 2019. The disease is characterized by chronic airway inflammation, reversible bronchoconstriction, and airway remodeling. Longitudinal studies have shown that current treatments for asthma (inhaled bronchodilators and corticosteroids) can reduce the frequency of exacerbations, but do not modify disease outcomes over time. Further, longitudinal studies in children to adulthood have shown that these treatments do not improve asthma severity or fixed airflow obstruction over time. In asthma, fixed airflow obstruction is caused by remodeling of the airway wall, but such airway remodeling also significantly contributes to airway closure during bronchoconstriction in acute asthmatic episodes. The goal of the current review is to understand what is known about the heterogeneity of airway remodeling in asthma and how this contributes to the disease process. We provide an overview of the existing knowledge on airway remodeling features observed in asthma, including loss of epithelial integrity, mucous cell metaplasia, extracellular matrix remodeling in both the airways and vessels, angiogenesis, and increased smooth muscle mass. While such studies have provided extensive knowledge on different aspects of airway remodeling, they have relied on biopsy sampling or pathological assessment of lungs from fatal asthma patients, which have limitations for understanding airway heterogeneity and the entire asthma syndrome. To further understand the heterogeneity of airway remodeling in asthma, we highlight the potential of in vivo imaging tools such as computed tomography and magnetic resonance imaging. Such volumetric imaging tools provide the opportunity to assess the heterogeneity of airway remodeling within the whole lung and have led to the novel identification of heterogenous gas trapping and mucus plugging as important predictors of patient outcomes. Lastly, we summarize the current knowledge of modification of airway remodeling with available asthma therapeutics to highlight the need for future studies that use in vivo imaging tools to assess airway remodeling outcomes.

Vascular Endothelial Growth Factor as a Putative Biomarker of Depression in Asthmatics with Reversible Airway Narrowing.

The vascular endothelial growth factor (VEGF) plays a pivotal role in process of angiogenesis in adults. If angiogenesis is not properly controlled, its deregulation may implicate it in various psychosomatic diseases states. The aim of our study was to reveal possible correlation between severity of depression in asthmatics with different degrees of airway narrowing and serum vascular endothelial growth factor levels. The study population included a total of 122 adult subjects: 82 patients with asthma (among them 42 patients with irreversible bronchoconstriction and 40 patients with reversible bronchoconstriction) and 40 healthy participants as a control group. The standardized Beck Depression Inventory (BDI) was used to estimate the depression symptoms. Enzyme-linked immunosorbent assay (ELISA) was used to assess the VEGF serum concentration in all participants. There was a significant difference in depression symptoms in asthmatics with reversible (p = 0.0432) and irreversible airway obstruction (p = 0.00005) in comparison to control group and between these two subgroups of asthmatics (p = 0.0233). Obtained results revealed significant correlation between level of depression and mean VEGF serum concentration in asthmatics with reversible airway obstruction (p = 0.0202). There was no difference between enhanced depression symptoms and VEGF serum concentration in patients with irreversible airway obstruction nor in the total group of asthmatics (in both p > 0.05). The relationship between asthma severity and depression symptoms seems to be certain. VEGF might be considered as a putative biomarker of depression in asthmatics, mainly those with reversible airway narrowing.

The Relationship Between Vitamin D and Asthma Exacerbation.

Asthma is a chronic airway inflammatory condition that affects millions of people worldwide. It presents with reversible bronchoconstriction that makes it difficult for patients to breathe. Asthma flare-ups have several triggers, but the symptoms are similar, including wheezing, coughing, shortness of breath, and chest tightness. Severe asthma exacerbation is described as symptomatic asthma that is unresponsive to inhaled asthma medications and is only responsive to steroids in oral or intravenous forms. Asthma-related deaths occur during episodes of asthma exacerbation.Vitamin D is a steroid-derived vitamin produced by the body and found in some foods. Administration of doses of vitamin D can also help maintain an adequate level of the vitamin. Vitamin D plays a vital role in regulating the level of calcium in the body and bone remodeling processes. It also has an immunomodulatory effect on innate and adaptive immunity within the body and that partially explains its links to inflammation-induced epithelial changes seen in asthma.We conducted this literature review by selecting articles from PubMed and Cumulated Index to Nursing and Allied Health Literature (CINAHL) Plus databases to investigate the relationship between vitamin D level and asthma exacerbation. From the studies, we found that asthmatic patients have low vitamin D levels during an asthma exacerbation. However, supplementing vitamin D may not reduce the rates of asthma exacerbation except in adult asthmatic patients with low levels of vitamin D.

The novel TRPA1 antagonist BI01305834 inhibits ovalbumin-induced bronchoconstriction in guinea pigs

BackgroundAsthma is a chronic respiratory disease in which the nervous system plays a central role. Sensory nerve activation, amongst others via Transient Receptor Potential Ankyrin 1 (TRPA1) channels, contributes to asthma characteristics including cough, bronchoconstriction, mucus secretion, airway hyperresponsiveness (AHR) and inflammation. In the current study, we evaluated the efficacy of the novel TRPA1 antagonist BI01305834 against AHR and inflammation in guinea-pig models of asthma.MethodsFirst, a pilot study was performed in a guinea-pig model of allergic asthma to find the optimal dose of BI01305834. Next, the effect of BI01305834 on (1) AHR to inhaled histamine after the early and late asthmatic reaction (EAR and LAR), (2) magnitude of EAR and LAR and (3) airway inflammation was assessed. Precision-cut lung slices and trachea strips were used to investigate the bronchoprotective and bronchodilating-effect of BI01305834. Statistical evaluation of differences of in vivo data was performed using a Mann–Whitney U test or One-way nonparametric Kruskal–Wallis ANOVA, for ex vivo data One- or Two-way ANOVA was used, all with Dunnett’s post-hoc test where appropriate.ResultsA dose of 1 mg/kg BI01305834 was selected based on AHR and exposure data in blood samples from the pilot study. In the subsequent study, 1 mg/kg BI01305834 inhibited AHR after the EAR, and the development of EAR and LAR elicited by ovalbumin in ovalbumin-sensitized guinea pigs. BI01305834 did not inhibit allergen-induced total and differential cells in the lavage fluid and interleukin-13 gene expression in lung homogenates. Furthermore, BI01305834 was able to inhibit allergen and histamine-induced airway narrowing in guinea-pig lung slices, without affecting histamine release, and reverse allergen-induced bronchoconstriction in guinea-pig trachea strips.ConclusionsTRPA1 inhibition protects against AHR and the EAR and LAR in vivo and allergen and histamine-induced airway narrowing ex vivo, and reverses allergen-induced bronchoconstriction independently of inflammation. This effect was partially dependent upon histamine, suggesting a neuronal and possible non-neuronal role for TRPA1 in allergen-induced bronchoconstriction.

Physical fitness and quality of life in adolescents with asthma and fixed airflow obstruction.

To compare adolescents with asthma and FAO and adolescents with asthma without FAO in terms of aerobic fitness, PAL, muscle strength, and health-related quality of life (HRQoL). This cross-sectional study included adolescents with asthma, both sexes, and aged 12-18 years. They were divided into two groups: FAO and non-FAO groups. The adolescents were diagnosed with asthma according to the Global Initiative for Asthma guidelines and underwent optimal pharmacological treatment for at least 12 months. FAO was diagnosed when the forced expiratory volume in the first second/forced vital capacity ratio was below the lower limit of the normal range after optimal treatment. Aerobic fitness, PAL, peripheral and respiratory muscle strength, and HRQoL were evaluated. No significant differences were observed between FAO and non-FAO groups regarding the peak oxygen uptake (34.6 ± 8.5 vs. 36.0 ± 8.4 mLO2 /min/kg), sedentary time (578 ± 126 vs. 563 ± 90 min/day), upper limb muscle strength (29.1 ± 5.9 vs. 28.1 ± 5.7 kilograms of force [kgf]), lower limb muscle strength (42.8 ± 8.6 vs. 47.6 ± 9.6 kgf), or HRQoL (5.1 ± 1.3 vs. 4.7 ± 1.4 score; p > .05). However, the FAO group exhibited a higher maximal expiratory pressure than the non-FAO group (111.5 ± 15.5 vs. 101.5 ± 15.0 cmH2 O, respectively). Our results suggest that FAO does not impair aerobic fitness, PAL, peripheral muscle strength, or HRQoL in adolescents with asthma. Furthermore, adolescents with asthma were physically deconditioned.

Developments in asthma incidence and prevalence in Alberta between 1995 and 2015

BackgroundAsthma is a chronic respiratory disease characterized by reversible bronchoconstriction and airway inflammation. According to Statistics Canada in 2014, 8.1% of Canadians aged 12 and older reported having asthma diagnosed by a health care professional. Therefore, in 2014 there were an estimated 274,661 persons with asthma in Alberta. Most epidemiological studies estimate prevalence and incidence using survey-based data, which has limitations. The Ontario Asthma Surveillance Information System (OASIS) group has developed and validated an algorithm for epidemiologic asthma studies using provincial health databases. In Alberta, there are some studies using provincial databases, but most are restricted to emergency department visits and do not represent the entire asthma population. Using the validated asthma definition for epidemiologic studies, we performed an analysis of the Alberta Health administrative databases to investigate and report province-wide asthma prevalence, incidence and mortality in Alberta from 1995 to 2015.MethodsData from administrative databases, provided by Alberta Health, was analyzed to determine age and sex specific prevalence, incidence and mortality of the asthma population. The population cohort was all individuals residing in the province of Alberta, ages 0 to 99 from 1995–2015. Kendall’s Tau coefficient test was used to ascertain whether the observed trends were statistically significant.ResultsBetween 1995 and 2015, the age-standardized incidence of asthma decreased by more than 50% in both males and females. Prevalence, however, increased threefold over the 20 years (for both genders) from 3.9 to 12.3% (Tau = 1.00, p < 0.0001) in females and from 3.5 to 11.6% (Tau = 1.00, p < 0.0001) in males. Thus, in 2015 there were 496,927 people with asthma in Alberta. All-cause mortality in the asthma population decreased over time, in both females (Tau = − 0.71, p < 0.0001) and males (Tau = − 0.69, p = 0.0001). For the last several years, all-cause mortality was higher in those with asthma. There were ~ 7 deaths/1000 in the population with asthma versus ~ 5 deaths/1000 in those without asthma.ConclusionsThe incidence of asthma decreased in both females and males while prevalence continued to increase, although at a slower rate than previously. All-cause mortality in asthma patients was higher than in those without asthma, but both decreased over time.

Risk factors for fixed airflow obstruction in children and adolescents with asthma: 4-Year follow-up.

Asthma is a disease with reversible bronchoconstriction; however, some patients develop fixed airflow obstruction (FAO). Previous studies have reported the incidence and risk factors of FAO in adults; however, the corresponding factors in children remain poorly understood. To evaluate the incidence and risk factors of FAO in children and adolescents with asthma. Observational and prospective cohort study with a 4-year follow-up of clinically stable patients with asthma (from 6-8years old). Anthropometric data, history of asthma, number of hospitalizations, frequent exacerbations, asthma severity, asthma control, inhaled corticosteroid dose, atopy, and lung function were analyzed as potential risk factors for FAO. FAO was defined by a ratio of the forced expiratory volume in the first second to the forced vital capacity below the lower limit of normal, even after inhaled and oral corticosteroid treatment. Four hundred and twenty-eight patients were recruited, and 358 were analyzed. The FAO incidence in children and adolescents with asthma was 9.5% (n = 34), starting at 10 years of age. Age, body mass index, hospitalizations for asthma, bronchodilator response, frequent exacerbations, length of exacerbations, and asthma severity were associated with FAO. Frequent exacerbations (odds ratio [OR] = 4.0; 95% confidence interval [CI] = 1.3-11.7) and asthma severity categorized as steps 4 to 5 (OR = 3.5; 95% CI = 1.6-7.6) remained risk factors. Frequent exacerbations and asthma severity are the risk factors for FAO in children and adolescents with asthma.

The -2549 -2567 del18 Polymorphism in VEGF and Irreversible Bronchoconstriction in Asthmatics.

While the importance of vascular endothelial growth factor (VEGF) in the pathogenesis of several diseases (eg, neoplasms) has been proven, its role in asthma, especially in terms of the potential associations between genetic variants of VEGF and airway remodeling, has received relatively little attention. Objectives: This study aimed to evaluate the possible connection between a genetic factor, ie, the polymorphism del/ins in the VEGF promoter region, and airway remodeling potential in asthmatics with and without irreversible bronchoconstriction. The study population comprised 82 patients with asthma (of whom 42 had irreversible bronchoconstriction) and a group of 40 controls. DNA was isolated from peripheral blood leukocytes. Polymerase chain reaction was used to type the VEGF (18-bp deletion/insertion) gene polymorphism at loci -2549 -2567. Other factors (ie, smoking, disease duration) were also taken into consideration. The del/del genotype was found in 74.39% of patients with asthma (P=.031; OR=2.38), 80.95% of patients with irreversible bronchoconstriction (P=.012; OR=3.48), and 67.5% patients with reversible bronchoconstriction (P=.251; OR=1.70). The proportion of smokers to nonsmokers was higher (P=.032) and disease duration was longer (P=.041) in patients with irreversible bronchoconstriction than in those with reversible bronchoconstriction. Our results showed that the risk of irreversible bronchoconstriction in asthmatics was associated with the presence of the del18 genotype at the -2549 -2567 position in the promoter region of the VEGF gene, as were disease duration and other factors such as smoking.

VEGF serum concentration and irreversible bronchoconstriction in adult asthmatics.

Vascular endothelial growth factor (VEGF) is an angiogenic, heparin-binding glycoprotein playing an important role in the pathogenesis of many diseases and disorders, including asthma. It has been reported that increased VEGF serum concentration is a biomarker of neovascularization, which could suggest that higher VEGF expression may be relevant to asthmatics with airway remodeling and irreversible bronchoconstriction. The aim of this study was to assess the possible association between VEGF serum concentration and irreversible bronchoconstriction in adult patients with a diagnosis of asthma. This study involved 82 adult patients with asthma (42 persons with and 40 persons without irreversible bronchoconstriction) and 40 healthy adult controls. Vascular endothelial growth factor serum concentration was analyzed using enzyme-linked immunosorbent assay (ELISA). Vascular endothelial growth factor serum concentration in patients with asthma was higher than in healthy controls (p = 0.0131), particularly in those from the subgroup of irreversible bronchoconstriction (p = 0.0133). The rising tendency was confirmed using the Kruskal–Wallis rank sum test that showed a significant difference (p = 0.0374) in VEGF values among the 3 groups examined: healthy controls (Me = 246.6 pg/mL), asthmatics with reversible bronchoconstriction (Me = 288.6 pg/mL) and asthmatics with irreversible bronchoconstriction (Me = 340.6 pg/mL). However, the direct comparison between the 2 asthmatics groups (reversible vs irreversible bronchoconstriction) did not show a statistically significant difference (p = 0.5521). Increased VEGF serum concentration is characteristic of patients with asthma, especially those with irreversible bronchoconstriction.

Lung Microbiome Is Influenced by the Environment and Asthmatic Status in an Equine Model of Asthma.

There is evidence that the lung microbiome differs between patients with asthma and healthy humans, but the effect of environmental conditions and medication is unknown and difficult to study. Equine asthma is a naturally occurring chronic airway disease characterized by reversible airway inflammation and bronchoconstriction upon exposure to inhaled antigens. In the present study, we evaluated the effect that environmental conditions and disease status have on pulmonary, nasal, and oral microbiomes. Six asthmatic and six healthy horses were studied while at pasture ("low antigen exposure"), as well as when being housed indoors and fed good-quality hay ("moderate exposure") and poor-quality hay ("high exposure"). At each time point, lung function was recorded; BAL, oral, and nasal rinses were collected; and 16S rRNA gene sequencing was performed. Asthmatic horses developed airway obstruction and inflammation under moderate and high antigen exposure conditions, whereas nonasthmatic horses showed mild inflammation under high antigen exposure, without bronchoconstriction. Lung, oral, and nasal communities clustered by environmental condition, but only lung communities were different between healthy and asthmatic horses. The association between asthma and lung microbiome was strongest in horses under moderate antigen exposure. Pulmonary, oral, and nasal microbiomes are influenced by environmental conditions, but only the pulmonary microbiome differs between horses with and without asthma. This difference, seen mainly when airway inflammation was present in horses with asthma but not in control animals, suggests that the altered lung microbiome in asthma might not be inherent but coincident with inflammation.

Eicosanoid Control Over Antigen Presenting Cells in Asthma.

Asthma is a common lung disease affecting 300 million people worldwide. Allergic asthma is recognized as a prototypical Th2 disorder, orchestrated by an aberrant adaptive CD4+ T helper (Th2/Th17) cell immune response against airborne allergens, that leads to eosinophilic inflammation, reversible bronchoconstriction, and mucus overproduction. Other forms of asthma are controlled by an eosinophil-rich innate ILC2 response driven by epithelial damage, whereas in some patients with more neutrophilia, the disease is driven by Th17 cells. Dendritic cells (DCs) and macrophages are crucial regulators of type 2 immunity in asthma. Numerous lipid mediators including the eicosanoids prostaglandins and leukotrienes influence key functions of these cells, leading to either pro- or anti-inflammatory effects on disease outcome. In this review, we will discuss how eicosanoids affect the functions of DCs and macrophages in the asthmatic lung and how this leads to aberrant T cell differentiation that causes disease.

Mitigation of airways responsiveness by deep inflation of the lung.

Stretching activated strips of airway smooth muscle (ASM) significantly affects both active force and stiffness due to a temporary reduction of the proportion of cycling myosin cross bridges that are bound to their actin binding sites. For the same reason, stretch applied to ASM in situ by a deep inflation (DI) of the lungs is one of the most potent means of reversing bronchoconstriction. When the DI is sufficiently large, however, and is applied while bronchoconstriction is in the process of developing, the subsequent depression in airway resistance is more persistent than can be attributed simply to temporary detachment of ASM cross bridges. In the present study, we use a computational model to demonstrate that this DI-induced ablation of airway responsiveness can be explained by a dose-dependent reduction in the number of cross bridges available to bind to actin when the ASM in the airway wall is stretched above a critical threshold strain and that this disruption of the contractile apparatus recovers over an order of magnitude longer time scale than that of the simple reattachment of unbound cross bridges. NEW & NOTEWORTHY The mechanisms by which deep inflation of the lung reverse bronchoconstriction and affect subsequent airway responsiveness have important potential implications for asthma, yet remain controversial. This study uses computational modeling to posit a mechanism by which sufficiently vigorous inflations applied during active bronchoconstriction not only transiently reverse bronchoconstriction, but also reduce subsequent airways responsiveness for a period of time. Fitting the model to published data in mice supports this notion.

Endobronchial thermoplasty for asthma.

Asthma is an incurable chronic disease affecting approximately 24 million people in the United States. The hallmark features of asthma are reversible airflow obstruction, airway hyperresponsiveness, airway inflammation, bronchoconstriction, and excessive mucus secretion. Clinical symptoms include episodic or persistent breathlessness, wheezing, cough, or chest tightness/pressure. Forty-five percent of asthmatics continue to have yearly exacerbations and the disease is responsible for approximately 3,600 annual deaths. Pharmacologic advancements have continued to grow as the individual phenotypes of asthma are better delineated but there continues to be small population of asthmatics that are less responsive to pharmacologic therapy. Bronchial thermoplasty (BT) is an innovative procedure targeted primarily at decreasing airway smooth muscle (ASM) which is considered by some to be a vestigial organ. Decreasing the ASM bulk decreases hyperresponsiveness and bronchoconstriction leading to decreased exacerbations, decreased cost on the healthcare system, and improvement in patient quality of life.

Cellular Na+ handling mechanisms involved in airway smooth muscle contraction (Review).

A decrease in bronchial diameter is designated as bronchoconstriction (BC) and impedes the flow of air through the airway. Asthma is characterized by inflammation of the airways, reversible BC and nonspecific hyperreactivity. These last two symptoms are dependent on airway smooth muscle. Stimuli that trigger contraction can be characterized as chemical (neurotransmitters, cytokines and terpenoids) and physical (volume inspired, air pressure). Both stimuli activate signaling pathways by acting on membrane proteins and facilitating the passage of ions through the membrane, generating a voltage change and a subsequent depolarization. Na+ plays an important role in preserving the resting membrane potential; this ion is extracted from the cells by the Na+/K+ ATPase (NKA) or introduced into the cytoplasm by the Na+/Ca2+ exchanger (NCX). During depolarization, Na+ appears to accumulate in specific regions beneath the plasma membrane, generating local concentration gradients which determine the handling of Ca2+. At rest, the smooth muscle has a basal tone that is preserved by the continuous adjustment of intracytoplasmic concentrations of Ca2+ and Na+. At homeostasis, the Na+ concentration is primarily dependent on three structures: the NKA, the NCX and non-specific cation channels (NSCC). These three structures, their functions and the available evidence of the probable role of Na+ in asthma are described in the present review.

Feline lower airway disease: asthma and beyond

Lower airway disease is common in cats and includes a spectrum of disease from feline asthma to chronic bronchitis, both presenting with a chronic cough. Asthmatic cats may additionally suffer reversible bronchoconstriction causing dyspnoea. Diagnosis is made via thoracic radiographs and bronchoalveolar lavage, with other conditions causing similar clinical signs, such as congestive heart failure, having been excluded. The mainstay of treatment is corticosteroids, initially orally but followed by inhalational therapy, which is well tolerated and should be introduced slowly while providing owners lots of support and guidance. Bronchodilators may be useful for cats with asthma particularly during an acute episode, and triggering allergens should be avoided.

Irritable Bowel Syndrome and Bronchial Asthma: Are They Associated in Indian Population ?

Irritable Bowel Syndrome (IBS), a common gastrointestinal (GI) disorder has been linked with asthma implying a clue to its pathophysiology as being some form of allergic response. Previous studies from other parts of the world have shown both the presence as well as an absence of an association between them. We conducted a cross-sectional study to find an association between IBS and asthma, in an Indian cohort. Seventy patients of IBS diagnosed by exclusion and ROME III criteria with a matched control group were questioned for GI, respiratory symptoms along with their spirometry analysis. Those having reversible bronchoconstriction were categorized as asthmatic. The prevalence of asthma in the IBS group of 16 females and 54 males was 12 (17.14%) as compared to 14 (20%) in control group. Chi-square test revealed the Odds Ratio (OR) for prevalence of asthma in IBS as 0.828 with 95% Confidence Interval (CI) between 0.320 and 2.121 (p=0.664) which was non-significant (p>0.05). This study denies the presence of association between IBS and asthma among Indian cohorts and suggests that regional variations are present in the above association.

Critical role of Toll-like receptors in pathophysiology of allergic asthma

Allergic asthma is an airway disease, characterized by reversible bronchoconstriction, chronic inflammation of the airway, and thickness of smooth muscle in the respiratory tract. Asthma is orchestrated by an excessive Th2-adaptive immune response, in which innate immunity plays a key role. Recently TLRs have received more and more attention as they are central to orchestrate the innate immune responses. TLRs are localized as integral membrane or intracellular glycoproteins with those on the cell surface sensing microbial antigens and the ones, localized in intracellular vesicles, sensing microbial nucleic acid species. Having recognized microbial antigens, TLRs conduct the immune response towards a pro- or anti-allergy response. As a double-edged sword, they could initiate either harmful or helpful responses by the immune system in case of allergic asthma. In the current review, we will describe the role of TLRs and their signaling pathways in allergic asthma.

Misdiagnosis of asthma in schoolchildren.

A correct diagnosis of asthma is the cornerstone of asthma management. Few pediatric studies have examined the accuracy of physician-diagnosed asthma. We determined the accuracy of parent reported physician-diagnosed asthma in children sampled from a community cohort. Nested case-control study that recruited 203 children, aged 9-12, from a community-based sample. Three groups were recruited: asthma cases had a parental report of physician-diagnosed asthma, symptomatic controls had respiratory symptoms without a diagnosis of asthma, and asymptomatic controls had no respiratory symptoms. All participants were assessed and assigned a clinical diagnosis by one of three study physicians, and then completed spirometry, methacholine challenge, and allergy skin testing. The reference standard of asthma required a study physician's clinical diagnosis of asthma and either reversible bronchoconstriction or a positive methacholine challenge. Diagnostic accuracy, sensitivity and specificity were calculated for parent-reported asthma diagnosis compared to the reference standard. One hundred two asthma cases, 52 controls with respiratory symptoms but no asthma diagnosis, and 49 asymptomatic controls were assessed. Physician agreement for the diagnosis of asthma was moderate (kappa 0.46-0.81). Compared to the reference standard, 45% of asthma cases were overdiagnosed and 10% of symptomatic controls were underdiagnosed. Parental report of physician-diagnosed asthma had 75% sensitivity and 92% specificity for correctly identifying asthma. There is significant misclassification of childhood asthma when the diagnosis relies solely on a clinical history. This study highlights the importance of objective testing to confirm the diagnosis of asthma. Pediatr Pulmonol. 2017;52:293-302. © 2016 Wiley Periodicals, Inc.