Reversible Bronchial Obstruction Research Articles

Reversibility of bronchial obstruction in patients with primary ciliary dyskinesia to justify correction of inhalation therapy

Purpose. To assess the reversibility of bronchial obstruction in patients with primary ciliary dyskinesia in groups with and without concomitant allergic inflammation, with the aim of a differentiated approach to inhalation therapy and the validity of prescribing bronchodilators.Material and methods. Retrospective analysis of the results of FEV1 before and after inhalation of a bronchodilator and study of the dependence of the reversibility of obstruction on the presence of atopy markers.Results. Of 100 patients, 63% (n=63) had atopy markers; 37% (n=37) did not have these markers (p≤0.05). When comparing the FEV1 indicator in children with the presence of allergic burden (n=63) and in the absence of it (n=37), it was found that in patients with markers of atopy, obstructive changes identified during spirometry were 14.2% more common ( p≤0.05). Reversibility of bronchial obstruction was recorded in 24% (n=24), of which 87.5% (n=21) of patients had markers of atopy (p≤0.05). In children with concomitant allergic burden and a decrease in FEV1, reversibility of obstruction was detected in 48.4% (n=15) of cases (p≤0.05). It was revealed that in patients with the presence of atopy markers and a decrease in FEV1≤80%, reversibility of obstruction occurs 42.8% more often compared to the group of patients with a normal level of FEV1 (p≤0.05).Conclusions. The vast majority of patients with primary ciliary dyskinesia (n=63) have markers of atopy, mainly due to an isolated increase in total IgE in the blood serum (p≤0.05). A decrease in FEV1≤80% in children with allergies was detected 14.2% more often compared to the group of children without it (p≤0.05). In the vast majority of patients with an allergic phenotype, reversibility of obstruction was observed after a test with a bronchodilator. Thus, all patients with primary ciliary dyskinesia and the presence of atopy markers are recommended to undergo a test with a bronchodilator, and if reversibility of obstruction is detected, it is advisable to add a bronchodilator drug to therapy.

An unusual case of upper airways obstruction

Tracheal stenosis poses a diagnostic challenge that can mimic other respiratory pathologies, particularly bronchial asthma. It is characterized by a narrowing of the tracheal caliber, leading to respiratory symptoms such as dyspnea, cough, and wheezing. However, these manifestations can overlap with those of bronchial asthma, making the differential diagnosis a challenging yet crucial task for an appropriate therapeutic approach. This study aims to underscore the importance of a comprehensive clinical approach, utilizing bronchoscopy and global spirometry with bronchodilator reversibility testing, to differentiate tracheal stenosis from bronchial asthma, thereby contributing to accurate and timely surgical treatment. Bronchoscopy stands as a cornerstone in investigating tracheal stenosis, allowing for a direct assessment of the site, extent, and nature of the stenosis. Endoscopic observation of the morphological characteristics of the stenosis, such as concentric narrowing or mucosal irregularities, can guide towards a more precise diagnosis. Asthma, characterized by a reversible bronchial obstruction, responds positively to bronchodilators, whereas tracheal stenosis shows a limited or absent response.

Insights from Overviewing Selective International Guidelines for Pediatric Asthma.

Asthma is a chronic atopic and inflammatory bronchial disease characterized by recurring symptoms and, episodic reversible bronchial obstruction and easily triggered bronchospasms. Asthma often begins in childhood. International guidelines are widely accepted and implemented; however, there are similarities and differences in the management approaches. There is no national guideline in many cities in Asia. This review aims to provide a practical perspective on current recommendations in the management of childhood asthma, specifically in the following aspects: diagnosis, classification of severity, treatment options, and asthma control, and to provide physicians with up-to-date information for the management of asthma. We used the PubMed function of Clinical Queries and searched keywords of "Asthma", "Pediatric," AND "Guidelines" as the search engine. "Clinical Prediction Guides", "Etiology", "Diagnosis", "Therapy," "Prognosis," and "Narrow" scope were used as filters. The search was conducted in November 2022. The information retrieved from this search was used in compiling the present article. Diagnosis is clinically based on symptom pattern, response to therapy with bronchodilators and inhaled corticosteroids, and spirometric pulmonary function testing (PFT). Asthma is classified in accordance with symptom frequency, peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), atopic versus nonatopic etiology, where atopy means a predisposition toward a type 1 hypersensitivity reaction. Asthma is also classified as intermittent or persistent (mild to severe). Unfortunately, there is no disease cure for asthma. However, symptoms can be prevented by trigger avoidance and suppressed with inhaled corticosteroids. Antileukotriene agents or long-acting beta-agonists (LABA) may be used together with inhaled corticosteroids if symptoms of asthma are not controlled. Rapidly worsening symptoms are usually treated with an inhaled short-acting beta-2 agonist (SABA, e.g., salbutamol) and oral corticosteroids. Intravenous corticosteroids and hospitalization are required in severe cases of asthma attacks. Some guidelines also provide recommendations on the use of biologics and immunotherapy. Asthma is diagnosed clinically, with supporting laboratory testing. Treatment is based on severity classification, from intermittent to persistent. Inhaled bronchodilator and steroid anti-inflammatory form the main stay of management.

An unusual case of upper airways obstruction: What if it's not asthma?

Tracheal stenosis poses a diagnostic challenge that can mimic other respiratory pathologies, particularly bronchial asthma. It is characterized by a narrowing of the tracheal lumen, leading to respiratory symptoms such as dyspnea, cough, and wheezing. However, these manifestations can overlap with those of bronchial asthma, making the differential diagnosis a challenging yet crucial task for an appropriate therapeutic approach. This study aimsed to underscore the importance of a comprehensive clinical approach, using bronchoscopy and global spirometry with bronchodilator reversibility testing, to differentiate tracheal stenosis from bronchial asthma, thereby contributing to accurate and timely surgical treatment. Bronchoscopy stands as a cornerstone in investigating tracheal stenosis, allowing for a direct assessment of the site, extent, and nature of the stenosis. Endoscopic observation of the morphological characteristics of the stenosis, such as concentric narrowing or mucosal irregularities, can guide precise diagnosis. Asthma, characterized by reversible bronchial obstruction, responds positively to bronchodilators, compared with a minimal response in the context of tracheal stenosis.

Reversible Bronchial Obstruction in Primary Ciliary Dyskinesia.

Inhaled bronchodilators are frequently used among patients with primary ciliary dyskinesia (PCD), although neither the effectiveness nor the prevalence of their use is known, due to the paucity of relevant studies. This is a retrospective analysis of pre- and post-bronchodilator spirometry results, of patients with PCD from two centers. Correlations were examined of bronchodilator response, with asthma and atopy markers. Of 115 patients, 46 (40%) completed spirometry pre- and post-bronchodilation. Of these, 26 (56.5%) demonstrated reversible airway obstruction (increase in %FEV1 predicted ≥ 10%). Obstruction reversibility was not found to be associated with a family history of asthma, blood eosinophil level, elevated IgE, or atopy symptoms. Of the 46 patients who completed bronchodilator spirometry, 29 (63%) were regularly using bronchodilators and inhaled corticosteroids. More than half of patients with PCD presented with reversible airway obstruction, without any correlation to markers of personal or familial atopy. Inhaled bronchodilators and corticosteroid therapies are commonly used for treating PCD. Evaluating bronchodilator response should be considered, and its effectiveness should be further studied.

Is Bronchodilation Testing Routinely Useful in All Asthmatic Children?

Background: The reversibility of bronchial obstruction is needed to diagnose asthma. Bronchodilation (BD) testing is, therefore, used in asthma work-up. This study explored the benefit of performing BD testing in asthmatic children without bronchial obstruction. Methods: The study included 60 subjects with asthma and normal lung function, 13 (21.7%) females and 47 (78.3%) males; the mean age was 11.5 years, 26 were adolescents, and 34 were children. Lung function, symptoms, use of asthma medications, type 2 inflammation, and asthma control were assessed in all subjects. Results: Eleven (18%) subjects positively responded to BD testing. Fifty-five percent of subjects were uncontrolled based on Global Initiative for Asthma (GINA) criteria. The multivariate analysis identified 2 factors associated with a positive response to BD testing: FEV1 [odds ratio (OR) = 0.91) and ACT (OR = 0.79). Conclusions: This study showed that BD testing could give additional helpful information in clinical practice. In addition, uncontrolled asthma, based on GINA criteria, was prevalent in children with normal lung function.

Role of FEF25-75 in managing children with newly-diagnosed asthma in clinical practice.

BackgroundReversible bronchial obstruction characterizes asthma. Spirometry is the gold standard to assess airflow, and FEV1 is the most reliable parameter in this regard. However, many children with asthma have FEV1 within the normal range despite uncontrolled asthma and worsening. Therefore, FEF25-75 has been proposed as a valuable marker of early airflow impairment. This study aimed at investigating FEF25-75 in a cohort of children with newly diagnosed asthma.Methods381 children (122 females, mean age 11.6 years) were consecutively visited and had a new asthma diagnosis. In addition, Spirometry, type-2 phenotyping, asthma control assessment, and ACT were performed.Results72 (18.9%) asthmatic children had impaired FEF25-75, such as <65% of predicted. Low FEF25-75 was associated with lower FVC and FEV1/FVC values (OR 1.11 and 1.32, respectively). Children with normal FEV1 but impaired FEF25-75 had more frequently uncontrolled asthma (15.8% vs. 32.4%) than children with both parameters within the normal range.ConclusionsFEF25-75 deserves adequate and careful consideration in children with asthma, and the presence of impaired FEF25-75 values suggests a more compelling approach. (www.actabiomedica.it)

Molecular Targets for Biological Therapies of Severe Asthma: Focus on Benralizumab and Tezepelumab.

Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). In recent years several molecular effectors and signaling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic mono-clonal antibodies currently allow one to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. Pro-allergic immunoglobulin E (IgE) is the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed; today other targets are successfully being exploited by biological treatments for severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor, and IL-4 and IL-13 can be targeted by dupilumab. Besides these drugs, which are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing severe asthma management on a global level. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, which are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. The aim of the study is to review the immunopathology and treatment efficacy for severe asthma and focused on new biological agents with benralizumab (anti-IL-5) and tezepelumab (anti-TSLP).

MATRIX METALLOPROTEINASES AS MARKERS OF RESPIRATORY TRACT REMODELING AND POTENTIAL THERAPEUTIC TARGET IN PATIENTS WITH BRONCHIAL ASTHMA

It is evidently known that chronic inflammatory process in the bronchi of patients with bronchial asthma is associated with the emergence and progression of airway remodeling, resulting in irreversible obstruction. However, the exact mechanisms of connection between inflammation and airway remodeling are not very well understood and that is the reason for delay of development new specific targeted drugs aimed to inhibit the process of inflammation and remodeling. Therefore, our goal was aimed to analyze and systematize data on the role of matrix metalloproteinases in the occurrence of airway remodeling in patients with bronchial asthma and the possibility of therapeutic effects on this process. Materials and methods: search for information on the role and mechanisms of influence of matrix metalloproteinases on airway remodeling processes in patients with bronchial asthma and the possibility of its pharmacological correction in electronic databases such as PubMed and Google Scholar over the past 25 years. Matrix metalloproteinase-9 and tissue proteinase-1 inhibitor have been shown to play the most important role in airway remodeling in the presence of bronchial asthma, supported by numerous experimental and clinical studies. Much attention is paid to the comparison of these indicators in bronchoalveolar lavage, induced sputum and blood on the background of exacerbation and in the presence of a stable course of the disease. The analysis of their content depending on the severity of the course, dysfunction of external respiration and the degree of reversibility of bronchial obstruction. Studies of the possibility of drug effects on the content of remodeling markers have shown low clinical efficacy. The results are contradictory, but most of them prove the important role of matrix metalloproteinase-9, tissue protease inhibitor-1 and their relationship in the occurrence and progression of airway remodeling and, consequently, the severity of the disease, which dictates the need to develop new additional treatments.

Molecular Targets for Biological Therapies of Severe Asthma.

Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). Within this context, during the last years several molecular effectors and signalling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic antibodies currently allow to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. In addition to pro-allergic immunoglobulin E (IgE), that chronologically represents the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed, today other targets are successfully exploited by biological treatments of severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor. Moreover, dupilumab behaves as a dual receptor antagonist of pleiotropic interleukins 4 (IL-4) and 13 (IL-13). Besides these drugs that are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, also including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing the global scenario of severe asthma management. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, that are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. Such tailored strategies are thus allowing to successfully target the immune-inflammatory responses underlying uncontrolled T2-high asthma.

MicroRNA miR-21 and miR-146a expression in male with a combination of bronchial asthma and chronic obstructive pulmonary disease

Patients with a combination of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) crossed phenotype (CP) BA and COPD are a separate nosological group. CP BA and COPD is a multifactorial disease. There is a hypothesis that genetic control of CP BA and COPD development at the posttranscriptional level is carried out by regulation of gene expression involving microRNA (miR) miR-21 and miR-146a; these molecules can be considered as potential diagnostic markers of CP BA and COPD. The purpose of this study was to evaluate the expression of miR-21, miR-146a in male with a combination of BA and COPD compared to those with isolated BA and COPD. Materials . We examined male patients (n = 65) (n = 48: 19 patients with CP BA and COPD; 14 patients with BA and COPD) and control group (n = 17). All the patients underwent a comprehensive clinical-laboratory and instrumental examination. The expression of miR-21, miR-146a was estimated in peripheral blood by a real-time polymerase chain reaction. Results . CP BA and COPD have lower levels of miR-21 and miR-146a than the BA, COPD, and control groups. CP BA and COPD patients have low levels of miR-21 and miR-146a associated with shorter duration of the disease and the presence of comorbid pathology (hypertension, angina pectoris), revealed in patients with the disease debut at an older age. Low miR-21 was associated with lower reversibility of bronchial obstruction in these patients, despite eosinophilic inflammation in the bronchi. Conclusion . It has been demonstrated that within the framework of complex diagnostics of CP BA and COPD in males it is reasonable to evaluate miR-146a and miR-21 expression in peripheral blood. MicroRNA miR-146a and miR-21 are promising molecular targets for phenotype-specific therapy in males with CP BA and COPD.

A NEW PERSPECTIVE ON BRONCHIAL ASTHMA AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE OVERLAP: POTENTIAL DIAGNOSTIC CRITERIA

The aim: The aim of the research was to analyze the results of observation andexamination of COPD patients in order to identify a group of individualswith potentialasthma overlap. Materials and methods:We have conducted a two-stagedynamic investigation of 43 COPD patients during 3-8 years. The patients were divided into two groups: group 1 counted 30 individuals who presented with at least one episode of reversible bronchial obstruction (RBO) during the observation; group 2 - 13 individuals who presented with nonreversible bronchial obstruction (nonRBO). At the first stage, we conducted a clinical observations analysis and studied lung function examination records; at the second stage, we calculated the markers of allergic inflammation. Results: It was revealed that around 70% of COPD patients have occasional episodes of RBO. It was established that the level of blood eosinophils in these patients on the whole is rather low even in people with intermittent RBO, and the total IgE level appeared to be significantly higher in patients with intermittent RBO comparing to the level of this marker in patients who have nonRBO. Conclusions:COPD patients with intermittent RBO and high level of total IgE level form a group with potential asthma overlap.

Влияние комбинации короткодействующих β2-агониста и M-холинолитика на эффективность коронарного кровотока по данным аппланационной тонометрии у пациентов с хронической обструктивной болезнью легких

Background: bronchodilators are the major class of drugs prescribed for chronic obstructive pulmonary disease (COPD). Meanwhile, treatment strategies for obstructive lung disease using bronchodilators are continually discussed and reviewed, in particular, with regard to their potential effect on cardiovascular system. Aim: to evaluate the effect of the combination of a short-acting β2-agonist plus an anticholinergic medication (fenoterol 50 μg/dose + ipratropium bromide 20 μg/dose, 2 doses) on the efficacy of coronary blood flow in COPD patients. Patients and Methods: spirometry with bronchodilator testing (at least 12 hours after using the medication) was performed in 30 COPD patients. The efficacy of coronary blood flow was assessed by central subendocardial viability ratio (C_SEVR) measured by applanation tonometry which was performed before and 15, 30, and 60 min after using the bronchodilator. Oxygen saturation was measured at all stages of the study. Results: the combination of fenoterol and ipratropium bromide resulted in the increase of C_SEVR by 9.5 [3.3; 10.8]% in patients with low oxygen saturation at baseline due to heart rate reduction, diastolic lengthening, and oxygen level improvement. The timing of the effect was determined by the reversibility of bronchial obstruction. No effects of the combination of fenoterol and ipratropium bromide on central and peripheral blood pressure were reported. Conclusion: low oxygen saturation at baseline and reversible bronchial obstruction in COPD patients allow for a favorable predicted systemic effect of the combination of fenoterol and ipratropium bromide. When using in therapeutic dosages and according to recommended dosage regimen, this combination improves bronchopulmonary function, oxygen saturation, and the efficacy of coronary blood flow measured by applanation tonometry. KEYWORDS: chronic obstructive pulmonary disease, applanation tonometry, central subendocardial viability ratio, SEVR, bronchial obstruction, oxygen saturation. FOR CITATION: Punin D.A. Effect of the combination of a short-acting β2-agonist plus an anticholinergic drug on the efficacy of coronary blood flow measured by applanation tonometry in chronic obstructive pulmonary disease. Russian Medical Inquiry. 2020;4(4):199–206. DOI: 10.32364/2587-6821-2020-4-4-199-206.

Модель нейтрофильной бронхиальной астмы у мышей как инструмент для тестирования персонализированных лекарственных средств

Bronchial asthma is a chronic inflammatory disease of the respiratory tract characterized by reversible bronchial obstruction and bronchial hyperreactivity. The neutrophilic endotype of bronchial asthma is associated with an aggressive course of the disease, severe tissue destruction and a low response to standard corticosteroid therapy. All of the above indicates the need to create new drugs for the treatment of neutrophilic asthma, which requires adequate animal models of this disease. We have proposed a protocol for the induction of experimental neutrophilic bronchial asthma in mice, which includes intraperitoneal immunization with a mixture of a model allergen of ovalbumin and Freund's adjuvant followed by aerosol challenge with the same allergen mixed with the lipopolysaccharide. This approach made it possible to reproduce the main manifestations of neutrophilic bronchial asthma: the production of IgE allergen-specific antibodies, the development of bronchial hyperreactivity, respiratory tract remodeling and the lung tissue infiltration with neutrophils. bronchial asthma, murine model, neutrophils The work was supported by the Grant of the President of the Russian Federation (no. MD-1578.2019.4).

Clinical and laboratory characteristics of patients with cardiopulmonary comorbidence

Comorbidity of bronchial obstructive diseases and arterial hypertension (AH) is an important medico-social problem due to the increased incidence, the severity of complications, the tendency to increase mortality and disability of patients. However, the clinical characteristics and role of the major markers of inflammation in the pathogenesis of conditions such as chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) against AH and their impact on the course of the disease remain poorly understood.The aim of the study is to study the main clinical and laboratory parameters of patients with ACO and COPD with concomitant AH compared with each other and patients with isolated AH and with ACO without AH.Materials and methods. To participate in the study, we selected 100 patients with ACO on the background of AH, 30 patients with ACO without AH, 30 patients with COPD on the background of AH, 30 patients with AH. Examination of patients included: clinical methods - analysis of complaints and anamnesis of patients, standard clinical examination with measurement of blood pressure and heart rate, anthropometric study with the determination of body mass index (BMI), spirometric study with a test for reversibility of bronchial obstruction, the concentration of interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor α (TNF-α) and C-reactive proteine (CRP) in serum were determined by enzyme immunoassay.Results. Patients of the surveyed groups did not differ significantly in age and gender composition. There were no significant differences in smoking status and major indicators of respiratory function in the ACO and COPD groups, unlike the AH group. However, the FEV1 increase after bronchodilator inhalation was significantly higher in the ACO groups than in the COPD group and only AH. No significant differences were found between the study groups on TNF-α. At the same time, the group of patients with ACO on the background of AH was significantly different from the group of only ACO, COPD with AH and only AH in terms of CRP and IL-6; for IL-8 there was a significant difference compared with the groups with ACO and COPD with AH, and there were no significant differences with the AH group.Conclusions. The less prolonged exposure of the smoking factor with the background of bronchial asthma leads to pronounced changes in respiratory function, similar to changes in COPD with greater exposure to smoking. ACO patients have a better reversal of bronchial obstruction in response to bronchodilators than patients with COPD, which may indicate a potential better response of this group of patients to bronchodilator treatment. The course of ACO on the background of AH is accompanied by more pronounced chronic inflammation

The values of the modified&#x0D; bronchodilation test glycopyrronium to identify the reversibility of bronchial obstruction in patients with chronic obstructive pulmonary disease.

Proposed modification of a bronchodilation test with sequential use of rapidly acting bronchodilators: anticholinergic actions glycopyrronium bromide 50 μg and β2-agonist - salbutamol 400 mcg in patients with stable COPD. Modified bronchodilatation test (MBT), was performed in 48 patients with stable COPD, revealed signs of reversible bronchial obstruction more often than the standard BDT (in 76% of cases, against 25% in primary and 36% in the control groups, respectively). The magnitude of the bronchodilator effect glycopyrrolate, defined on spirometry, comparable to that in sbdt in patients with COPD. The degree of increase in FEV1, FVC, POS patients after MDT was significantly higher than that in the standard theatre (sbdt), which confirms the synergistic effect of double bronchodilatation. Holding mbdt is recommended for detection of reversibility of bronchial obstruction in patients with COPD.

Evaluation of pulmonary reexpansion in a porcine model of bronchial foreign body.

This study was designed to establish a porcine model of reversible obstruction of endobronchial foreign body (FB) and to assess the natural pulmonary reexpansion process using radiology and histopathology after removal of the bronchial FB. A metal stent was placed in the right lower lobe bronchial lumen of 15 pigs by bronchoscopy and removed after 2 weeks of stent retention. Animals were divided into two groups (group I and II), based on when they were sacrificed (week 2 or week 4) after stent removal. Pigs underwent computerized tomography scan to document pulmonary radiological changes. The lungs were harvested for electron microscopy examination, and the expression of pulmonary surfactant-associated protein A (SPA) was determined by immunohistochemistry. Thirteen (86.7%) animals successfully responded to the intervention. Atelectasis was formed by stent implantation within 2 weeks. The ratio of the residual atelectasis area was smaller in group II compared to that in group I (P < 0.01). The histological manifestations of experimental lungs were significantly improved in group II. Moreover, the expression of SPA in group II was higher compared to that in group I (P < 0.01). We have established a model of reversible bronchial FB obstruction in pigs that is both feasible and appropriate for evaluating the long-term process of pulmonary reexpansion after removal of FB. Bronchial metal FB retention for a period of 2 weeks could form atelectasis, and a natural pulmonary recovery process related to atelectasis takes approximately 4 weeks after removal of metal FB.

Asthma-COPD overlap syndrome: recent advances in diagnostic criteria and prognostic significance.

The term asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) has been proposed for individuals with features of both asthma and COPD. Several attempts have been done to define ACOS on the basis of medical history, symptoms, and functional findings. The main diagnostic criteria include airflow obstruction with a strong although incomplete reversibility to bronchodilation tests, a significant exposure to cigarette or biomass smoke, and a history of atopy or asthma. Additional diagnostic elements include eosinophilic airway and systemic inflammation, a good response to corticosteroid treatment, and a high concentration of exhaled nitric oxide. ACOS should be distinguished from asthma with not fully reversible bronchial obstruction due to airway remodeling, thus the lack of smoking exposure should exclude the diagnosis of ACOS. In patients without a documented history of asthma before 40 years of age, an increase in FEV1 after bronchodilator >400 mL should be required to diagnose ACOS. ACOS has been found to be associated with impaired physical performance, functional ability, and health-related quality of life. The prevalence of ACOS increases with aging, then it is relatively stable in elderly individuals (>65 years). Long-term mortality of subjects with ACOS is similar to COPD, and worse than asthma and healthy controls. Future research is still needed to improve the understanding and management of ACOS.

The neonatal methylome as a gatekeeper in the trajectory to childhood asthma.

Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth. We next discuss how this trajectory may be affected by prenatal environmental exposures. Finally, we examine in vitro studies that model the impact of asthma-associated exposures on the epigenome. All of these studies specifically surveyed human DNA methylation and involved a genome-wide component. In combination, their results broaden our understanding of asthma pathogenesis and the role the methylome plays in this process.

CD26 and Asthma: a Comprehensive Review.

Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma. Curiously, two serine proteases within the S9 family encoded by genes located on chromosome 2 appear to have a role in asthma: CD26/dipeptidyl peptidase 4 (DPP4) and DPP10. The aim of this review is to summarize the current knowledge about CD26 and to provide a structured overview of the numerous functions and implications that this versatile enzyme could have in this disease, especially after the detection of some secondary effects (e.g., viral nasopharyngitis) in type II diabetes mellitus patients (a subset with a certain risk of developing obesity-related asthma) upon CD26 inhibitory therapy.