Chronic Obstructive Airways Research Articles

Delayed positive COVID19 nasopharyngeal test, a case study with clinical and pathological correlation

BackgroundThere are various reasons for delayed positive nasopharyngeal PCR tests for coronavirus disease 2019 (COVID19) in not only asymptomatic but also severely diseased patients. The pathophysiological attributes are not known. We explore this possibility through a case report.Case presentationA 64-year-old male with history of pulmonary fungal infection, asthma and chronic pulmonary obstructive disease (COPD), diabetes, coronary artery disease presented with shortness of breath, fever and chest image of ground opacity, reticular interstitial thickening, highly suspicious for COVID19. However, nasopharyngeal swab tests were discordantly negative for four times in two weeks, and IgG antibody for COVID19 was also negative. However, serum IgE level was elevated. No other pathogens are identified. His symptoms deteriorated despite corticosteroid, antibiotics and bronchodilator treatment. Bronchoalveolar lavage (BAL) and open lung wedge biopsy were performed for etiology diagnosis. They demonstrated COVID19 viral RNA positive fibrosing organizing pneumonia with respiratory tract damage characterized by suspicious viral cytopathic effect, mixed neutrophilic, lymphoplasmacytic, histiocytic and eosinophilic inflammation and fibrosis besides expected asthma and COPD change. One week later, repeated COVID19 nasopharyngeal tests on day 40 and day 49 became positive.ConclusionOur case and literature review indicate that allergic asthma and associated high IgE level together with corticosteroid inhalation might contribute to the delayed positive nasopharyngeal swab in upper airway; COPD related chronic airways obstruction and the addition of fibrosis induced ventilator dependence and poor prognosis in COVID19 pneumonia, and should be therapeutically targeted besides antiviral therapy.

Anti-Inflammatory Effects of RTD-1 in a Murine Model of Chronic Pseudomonas aeruginosa Lung Infection: Inhibition of NF-κB, Inflammasome Gene Expression, and Pro-IL-1β Biosynthesis.

Vicious cycles of chronic airway obstruction, lung infections with Pseudomonas aeruginosa, and neutrophil-dominated inflammation contribute to morbidity and mortality in cystic fibrosis (CF) patients. Rhesus theta defensin-1 (RTD-1) is an antimicrobial macrocyclic peptide with immunomodulatory properties. Our objective was to investigate the anti-inflammatory effect of RTD-1 in a murine model of chronic P. aeruginosa lung infection. Mice received nebulized RTD-1 daily for 6 days. Bacterial burden, leukocyte counts, and cytokine concentrations were evaluated. Microarray analysis was performed on bronchoalveolar lavage fluid (BALF) cells and lung tissue homogenates. In vitro effects of RTD-1 in THP-1 cells were assessed using quantitative reverse transcription PCR, enzyme-linked immunosorbent assays, immunoblots, confocal microscopy, enzymatic activity assays, and NF-κB-reporter assays. RTD-1 significantly reduced lung white blood cell counts on days 3 (−54.95%; p = 0.0003) and 7 (−31.71%; p = 0.0097). Microarray analysis of lung tissue homogenates and BALF cells revealed that RTD-1 significantly reduced proinflammatory gene expression, particularly inflammasome-related genes (nod-like receptor protein 3, Mediterranean fever gene, interleukin (IL)-1α, and IL-1β) relative to the control. In vitro studies demonstrated NF–κB activation was reduced two-fold (p ≤ 0.0001) by RTD-1 treatment. Immunoblots revealed that RTD-1 treatment inhibited proIL-1β biosynthesis. Additionally, RTD-1 treatment was associated with a reduction in caspase-1 activation (FC = −1.79; p = 0.0052). RTD-1 exhibited potent anti-inflammatory activity in chronically infected mice. Importantly, RTD-1 inhibits inflammasome activity, which is possibly a downstream effect of NF-κB modulation. These findings support that this immunomodulatory peptide may be a promising therapeutic for CF-associated lung disease.

Case Report: Pulmonary sarcomatoid carcinoma in a female patient from Nepal

Sarcomatoid carcinoma of the lung is an uncommon subtype of non-small-cell lung cancer (NSCLC). Even in the early stages, pulmonary sarcomatoid carcinoma (PSC) has a dismal prognosis when compared to other kinds of NSCLC with a mean survival of 9-12 months and a five-year survival rate of around 20%. We present the case of a 68-year-old woman with a two-month history of shortness of breath and cough. Initial computed tomography (CT) scan showed features of interstitial lung disease with chronic obstructive airway changes. After 34 months, the patient's condition worsened with newer complaints of sore throat and hemoptysis. A repeat CT scan showed a ∼49x38x59mm size lesion in the superior segment of the left lower lobe. A core needle biopsy was performed, which revealed tumor cells consisting of irregular tubules and sarcomatoid components. The patient was started on chemotherapy. Unfortunately, she succumbed to her disease. Our case highlights the aggressiveness of PSC.

New Insights into the Role of NLRP3 Inflammasome in Pathogenesis and Treatment of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by chronic airway obstruction and emphysema. Accumulating studies have shown that the onset and development of COPD are related to an aberrant immune response induced by the dysregulation of a number of genetic and environmental factors, while the exact pathogenesis of this disease is not well defined. Emerging studies based on tests on samples from COPD patients, animal models, pharmacological and genetic data suggest that the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation is required in the lung inflammatory responses in the development of COPD. Although the available clinical studies targeting the inflammasome effector cytokine, IL-1β, or IL-1 signaling do not show positive outcomes for COPD treatment, many alternative strategies have been proposed by recent emerging studies. Here, we highlight the recent progress in our understanding of the role of the NLRP3 inflammasome in COPD and propose possible future studies that may further elucidate the roles of the inflammasome in the pathogenesis or the intervention of this inflammatory lung disease.

Large underreporting of COPD as cause of death-results from a population-based cohort study

BackgroundIn 2019, WHO estimated COPD to be the third leading cause of death in the world. However, COPD is probably underestimated as cause of death due to the well-known under-diagnosis. AimTo evaluate the proportion of and factors associated with COPD recorded as cause of death in a long-term follow-up of a population-based COPD cohort. MethodsThe study population includes all individuals (n = 551) with COPD defined as chronic airway obstruction (post-bronchodilator FEV1/FVC<0.70) + respiratory symptoms identified after re-examinations of four population-based cohorts. Mortality and underlying or contributing cause of death following ICD-10 classification were collected from the Swedish National Board of Health and Welfares register from date of examination in 2002–04 until 2016. ResultsThe study sample consisted of 32.3% GOLD 1, 55.9% GOLD 2, and 11.8% GOLD 3–4. The mean follow-up time was 10.3 (SD3.77) years and the cumulative mortality 45.0%. COPD (ICD-10 J43-J44) was recorded on 28.2% (n = 70) of the death certificates (11.1%, 25.7% and 57.1% by GOLD stage), whereof n = 35 had COPD recorded as underlying and n = 35 as contributing cause of death. To have COPD recorded as cause of death was independently associated with ex- and current smoking and a self-reported physician diagnosis of COPD, while male sex, overweight/obesity and higher FEV1% of predicted associated with the absence. ConclusionsCOPD was largely underreported cause of death. Even among those with severe/very severe disease, COPD was only mentioned on 57.1% of the death certificates.

Persistent Nasal Obstruction: An Expression of the Pro-Inflammatory State?

Introduction: During the first years of life, the oro-pharyngeal lymphoid tissue gradually increases in size, causing in some children difficulty breathing and often leading to surgical removal of the tonsils and adenoids. The objective of the study is to assess the effects of the Mediterranean diet in children who had chronic upper airway obstruction. Material and methods: This was a prospective study pre-test/post-test comparison. Eighty-seven patients from two to eight years old were recruited. A food reeducation program based on the Mediterranean diet was applied for one year. Clinical, therapeutic, and anthropometric variables were studied. Results: The degree of nasal obstruction decreased in 95.1% of the patients. After the nutritional intervention, the number of colds with bacterial complications decreased by 80.26%; 60.9% had no bacterial complications during the year of the study. The use of antibiotics decreased by 81.94%. Symptomatic treatment decreased by 61.2%. Most patients did not require surgical intervention, and clinical evolution suggested that it would no longer be necessary. Conclusions: We can conclude by saying that the application of the traditional Mediterranean diet could be effective in the prevention and treatment of persistent nasal obstruction, limiting pharmacological and surgical intervention in many of these patients.

BIOMARKERS OF INFLAMMATION AT BRONCHIAL ASTHMA IN CHILDREN WITH ALTERNATIVE DEBUT OF THE DISEASE

Objectives - to analyze the activity of the inflammatory process in the airways of childrenwith bronchial asthma depending on different onset of the disease.Material and methods. Keeping to the principles of bioethics a comprehensiveretrospective examination of 319 children suffering from BA was performed. In 257children (clinical group I) bronchial asthma developed against a background of chronicobstructive bronchitis. The second clinical group included 43 children, in whom asthmadebuted after community-acquired pneumonia. The third (III) clinical group consistedof 19 children in whom asthma was first verified after inpatient treatment for asthmaticstatus.Results. According to the severity of bronchial asthma, it was found that the representativesof the III clinical group, compared with other patients, significantly more often had a severecourse of the disease. For patients of the I clinical group in the debut it is characterizedby increased eosinophils and decreased neutrophil counts in sputum, for patients ofgroup II - increased eosinophils and epitheliocytes, but a decrease in lymphocytes, andfor children of clinical group III - low eosinophils sputum with a simultaneous increasein neutrophils. In particular, a statistically significant increase in the content of VEGF,a decrease in the content of cationic proteins, MMP-9, and interleukins-6, and -13 inthe sputum indicates the predominance of neoangiogenesis in children of clinical groupIII. Instead, in the representatives of the II clinical group the remodeling processes weremainly caused by the inflammatory process with the release of intracellular eosinophiliccationic proteins.Conclusion. These data indicate the discrete nature of the type and severity of theinflammatory process of the respiratory tract in the dynamics of observation in childrenof clinical comparison groups, which suggests the presence of certain phenotypicdifferences due to the alternative onset of the disease, which in its turn was determinedby different triggers. Such deviations of the inflammatory process indicate that patientswith asthma require a personalized approach to differentiated diagnostic monitoring andtargeted anti-inflammatory treatment, taking into account the peculiarities of the onsetof the disease.

Efficiency of bronchial asthma control in children of school age depending on the features of the disease debut

Objective. To assess the effectiveness of achieving and maintaining control of bronchial asthma in children during dynamic observation, depending on the characteristics of the onset of the disease.&#x0D; Material and methods. In order to study the peculiarities of the course and controllability of bronchial asthma in children, depending on the alternative onset of the disease, 319 children were comprehensively examined by the "experience-control" method in parallel groups using a simple random sample on the basis of the Regional Children's Clinical Hospital in Chernivtsi. In 257 patients (I clinical group), bronchial asthma developed on the background of chronic obstructive bronchitis, the II clinical group included 43 children in whom BA debuted after suffering community-acquired pneumonia, and the third (III) clinical group was formed by 19 children in whom BA was verified after inpatient treatment for status asthmaticus.&#x0D; Research results. It was shown that the representatives of the III clinical group, compared with other patients, probably more often had the phenotype of early asthma and severe disease, and the ratio of the chances of severe asthma in the future for these children compared with the cohort of group I was 6.8. According to the results of self-assessment of asthma control on standardized questionnaires GINA and AST, as well as using a clinical-instrumental assessment scale, it was found that the level of disease control in all groups was insufficient, and the distribution of children in clinical groups in group III relative to other patients with partially controlled and uncontrolled asthma predominated. The conducted standard anti-inflammatory basic treatment allowed to achieve certain positive changes in patients of clinical observation groups, and the representatives of the III clinical group required more active basic anti-inflammatory therapy, in particular, the volume of the 1st step in GINA compared to patients of the I group was prescribed twice less often, and the 4th - 6.9 times more often.&#x0D; Conclusion. Patients with the onset of bronchial asthma in the form of status asthmaticus further retain a worse level of control over the disease as compared to patients with chronic obstructive bronchitis or pneumonia in history. This cohort of patients requires a larger volume of basic treatment, as well as a personalized approach to prescribing therapy with the obligatory consideration of the characteristics of asthma onset.

Alpha-1 antitrypsin deficiency in the elderly: a case report

BackgroundGenerally, alpha-1 antitrypsin deficiency (AATD) is suspected in young patients with pulmonary emphysema or chronic obstructive pulmonary disease (COPD). Patients often suffer from diagnostic gaps and are misdiagnosed with chronic obstructive pulmonary disease (COPD), asthma, and airway hyperresponsiveness (AHR), as AATD may present with nonspecific respiratory symptoms. It is never too late to suspect AATD, especially in a patient with an unusual medical history. In recent years, evidence is beginning to emerge that there may be value in identifying and treating patients who do not already have deterioration of functional parameters.Case presentationWe describe a case of a 69-year-old Caucasian female patient, late diagnosis of AATD, with both severe bronchial hyperreactivity and numerous exacerbations due to the peculiar clinical history and the presence of a rare mutation; although not presenting forced expiratory volume in 1 second (FEV1) between 30 and 65%, the patient was treated with alpha-1 antitrypsin (AAT) augmentation therapy and achieved clinical and functional improvement.ConclusionAATD should always be suspected. The Alpha-1 Foundation recommendations for the diagnosis and management of AATD in adult patients indicate that treatment should be provided for patients with FEV1 between 30 and 65%. It may be useful to evaluate and treat patients based on clinical symptoms, even outside the established parameters, in particular cases.

Physician Palliative Education Associated With High Use of Hospice Care Service.

Background:Taiwan’s National Health Insurance provides coverage for palliative and hospice care. The following 10 types of diseases have been added to the National Health Insurance reimbursement regulation: end-stage cancer, motor neuron disease, organic psychosis, brain degeneration, heart failure, chronic airway obstruction diseases, other lung diseases, chronic liver disease and cirrhosis, acute renal failure, and chronic renal failure.Objective:This study aimed to determine the association between physicians’ palliative education and use of hospice care in hospitalized patients at the end of life.Design and Setting:A cross-sectional study in a Taipei community hospital.Participants:Patients who died between 2014 and 2019 were identified. The deceased had at least 1 of the 10 diseases covered by health insurance were included. Hospice care services included hospice ward care and hospice shared care. This study included 2,661 individuals. In total, 972 (36.5%) patients used hospice care services.Results:After adjusting for age, gender, and comorbidities, physicians’ palliative education was found to significantly associated with the use of hospice care (OR: 14.38, 95% CI: 10.90-18.98).Conclusions:Physicians’ palliative education was found to be an independent factor associated with higher use of hospice care. The findings suggest increasing palliative and hospice education among physicians so that they can ensure that their patients have high-quality end-of-life medical care in an aging society.

The Impact of Adenotonsillectomy on Sleep and Behavior of Children with Obstructive Sleep Apnea.

Adenotonsillar hypertrophy (ATHt) is a common cause of chronic airway obstruction (UAO) in children and may cause obstructive sleep apnea syndrome (OSAS). Surgical correction in the form of Adenotonsillectomy (AdTyb) may significantly improve the sleep and behavior patterns of children, and enhance their quality of life. To test the effect of adenotonsillectomy on sleep and behavioral disorders in children with adenotonsillar hypertrophy. Prospective observational study; children ≤ 14years diagnosed with symptomatic adenotonsillar hypertrophy planned for surgery were included. Parents were asked to complete Connor's revised parent rating scale and Children's sleep habit questionnaire pre-operatively and 3months after surgery. This was done to evaluate the children's sleep habits, disturbances and behavior. A total of 77 children were included in the study. The age range was 4 - 14years. Fifty-two were male and rest, female. There was a significant reduction in Sleep score after surgery (mean pre-operative sleep score 51.3 ± 8.9 vs. post-operative 37.29 ± 7.1; p value < 0.001). Similarly, there was a statistically significant improvement in the behaviour score also after surgery (mean pre-operative behavior score 28.96 ± 9.8 vs. post-operative 23.13 ± 7.9; p value < 0.001). The sleep and behaviour scores were not related to the age or gender of the participants. Adenotonsillar hypertrophy causes documentable sleep disturbances and obstructive sleep apnea leading to neurobehavioral issues in children. The standard of care is surgery which leads to significant improvement in these aspects and quality of life.

ACUTE NONCARDIOGENIC PULMONARY EDEMA FOLLOWING NEOSTIGMINE ADMINISTRATION IN THE ENDOTRACHEAL INTUBATION STATE AFTER TONSILLECTOMY

Acute pulmonary edema during the perioperative period can have various causes. A 20-year-old woman was admitted for tonsillectomy and adenoidectomy. She had nasal congestion for 2 months, chronic sinusitis with polyps, and diffuse lymphoid hyperplasia. A biopsy and peripheral blood smear were performed to rule out a lymphoma before surgery. We injected neostigmine 1.5 mg and glycopyrrolate 0.4 mg at the end of the surgery. Two minutes later, the secretion and peak airway pressure increased as well as the CO2 levels. The patient remained sedated and suctioning continued for approximately 20 min before extubation. The secretions reduced and there was an improvement in clinical symptoms as the pinkish foamy pattern became whitish. Presumed treatment of neostigmine hypersensitivity or surgery can be used to resolve perioperative chronic partial airway obstruction.

Effect of TRPV4 Polymorphisms on the Development of Airway Response to Increased Inspiratory Load

Alongside with inflammation, increased airway resistance is a key feature of obstructive lung diseases. The data accumulated up to date suggest that bronchoconstriction commonly observed in asthma or COPD is not only a symptom but serves as an important factor of the diseases’ pathogenesis. Mechanical deformation of the airways occurring during the episodes of bronchoconstriction or accompanying chronic airflow limitation may per se promote respiratory inflammation and remodeling, thus, forming a vicious cycle. The precise molecular mechanisms triggering the response to mechanical stress in the airways have not been established so far. In this regard, a particular attention is drawn to TRP channels – polymodal receptors sensitive to many physical and chemical stimuli including stretching and compression at cellular level. TRPV4 is a mechanosensitive channel abundantly expressed in the airway epithelium that was previously proved to participate in stretch-induced respiratory responses during mechanical ventilation. The aim of this study was to establish the effects of SNPs located in TRPV4 region on the airway response induced by inspiratory resistive breathing. The study enrolled 122 patients with asthma, 82 patients with COPD and 54 healthy subjects. All the participants underwent 5-min isocapnic (5% CO2) inspiratory resistive breathing with load at 45% of maximum inspiratory pressure. Specific airway conductance (sGaw) was measured by body plethysmography before and after the inspiratory load. Relative change (Δ) in sGaw by ≥20% was considered as a significant response. Six SNPs (rs7139451, rs11068434, rs3825394, rs3825396, rs6606743, rs3742034) were genotyped by LATE-PCR with melting analysis of molecular beacon probes. All the studied SNPs were in Hardy-Weinberg equilibrium. SNP rs3825396 located in intronic region of TRPV4 exerted significant effect on the airway response to mechanical stress. In general sample, carriers of the AG genotype had higher ΔsGaw (9.0 (-8.5-30.6)%) in comparison with the GG homozygotes (-6.4 (-20.0-11.9)%, p=0.01). This trend was evident in the subgroups of healthy subjects, asthma and COPD patients, although the difference was not significant due to reduced number of observations. Carriers of the AA genotype were absent both in our sample and in reference HapMap population. The AG genotype was found in 5.4%, 13.3% and 25.0% of subjects with ΔsGaw ≤-20%, -20%<ΔsGaw<20% and ΔsGaw ≥20%, respectively (p=0.01). The difference was even more significant when comparing only between cases with ΔsGaw ≥20% and ΔsGaw ≤-20% (p=0.007). This association retained after adjustment for sex, age and diagnosis in logistic regression model (adjusted OR 5.2 95%CI (1.3-20.6), p=0.02). We did not found significant associations with the airway response to mechanical stress for the other studied SNPs. In conclusion, we established that TRPV4 rs3825396 SNP may influence reaction of the respiratory tract to increased inspiratory load. This association seems to be independent of the presence of the obstructive airway pathology, although further verification on larger sample is required.

Віддалені наслідки перенесеного в дитячому віці епізоду синдрому Лайєлла

The article provides a review of literature on the long-term consequences of Lyell's syndrome (one of the forms of toxic epidermal necrolysis). Among them: chronic eczema with xerosis and itching, skin depigmentation, hypertrophic and keloid scars, nail lesions, eyes, including dry eye syndrome and chronic conjunctivitis with/without obliteration of the nasolacrimal canal, kidney disease, lung disease, Sjogren's syndrome, Hashimoto's thyroiditis and others. Clinical case. The authors present their clinical case of an 11-year-old girl who suffered from Lyell's syndrome at the age of 8 and has been observed for the past three years, share their clinical and laboratory-instrumental observations and treatment strategies. In particular, they report about the revision of the clinical diagnosis with which the girl was admitted to the OHMADYT hospital, from BA to chronic secondary obstructive bronchitis, the detection of chronic conjunctivitis with obliteration of the nasolacrimal canals, chronic sinusitis, secondary immune deficiency, keloid skin scars. Conclusions. Despite constant rehabilitation therapy and a significant improvement in the general condition of the girl, it was not possible to fully restore the function of mucociliary transport, as a result ventilation of small bronchi gradually deteriorates, bronchiectasis is observed in the basal segments of the right lung, a polyserial strain S. aureus is formed, which is constantly sown from the child's sputum; it was not possible to fully restore the patency of the nasolacrimal canals and achieve a stable remission of chronic sinusitis. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: Lyell's syndrome, children, Long-term consequences, chronic obstructive bronchitis, obesity, treatment.

Electrospun Nanofiber Mats for Filtering Applications-Technology, Structure and Materials.

Air pollution is one of the biggest health and environmental problems in the world and a huge threat to human health on a global scale. Due to the great impact of respiratory viral infections, chronic obstructive pulmonary disease, lung cancer, asthma, bronchitis, emphysema, lung disease, and heart disease, respiratory allergies are increasing significantly every year. Because of the special properties of electrospun nanofiber mats, e.g., large surface-to-volume ratio and low basis weight, uniform size, and nanoporous structure, nanofiber mats are the preferred choice for use in large-scale air filtration applications. In this review, we summarize the significant studies on electrospun nanofiber mats for filtration applications, present the electrospinning technology, show the structure and mechanism of air filtration. In addition, an overview of current air filtration materials derived from bio- and synthetic polymers and blends is provided. Apart from this, the use of biopolymers in filtration applications is still relatively new and this field is still under-researched. The application areas of air filtration materials are discussed here and future prospects are summarized in conclusion. In order to develop new effective filtration materials, it is necessary to understand the interaction between technology, materials, and filtration mechanisms, and this study was intended to contribute to this effort.

The bronchodilator test in patients with airway obstruction: the responsiveness of lung function parameters

Interpretation of bronchodilator (BD) test based on reaction of forced expiratory in one second (FEV 1). For assessing bronchodilator responsiveness of lung volumes, airway resistance remains largely unexplored. Therefore, we assessed the response of pulmonary function parameters to BD to reveal the most responsive parameter. 90 patients with chronic airway obstruction (61 male and 29 female; aged 55±11; post- BD FEV 1 was 63.1+18.3 % predicted) performed spirometry and static lung volume measurements before and after inhalation of BD. We calculated effect size (ES) for each parameter from the difference between two means divided by the standard deviation of baseline score. There was a significant increase both FVC and FEV 1by 8.2 and 12.3 % from baseline (p&lt;0.001). ES were 0.34 for FEV1 and 0.26 for FVC. The ES for lung volumes were from -0.07 (total lung capacity) to -0.31 (residual volume). The ES for sRtot (specific airway resistance) was -0.5 and ES for sGeff (specific effective airway conductance) was 0.95. The parameters of airway resistance and conductance were more responsive for the assessment of pulmonary function changes than spirometry and lung volumes parameters in patients with chronic airway obstruction.

Electroacupuncture inhibits IL-17/IL-17R and post-receptor MAPK signaling pathways in a rat model of chronic obstructive pulmonary disease

Interleukin (IL)-17, as a T-helper 17 cell (Th17) cytokine, plays a key role in chronic obstructive pulmonary disease (COPD) pathophysiology including chronic inflammation and airway obstruction, which lead to decreased pulmonary function. The aim of this study was to investigate the effect of acupuncture on IL-17, its receptor (IL-17R) and the mitogen-activated protein kinase (MAPK) signaling pathway, in a rat model of COPD. The COPD model was induced in Sprague Dawley rats by exposure to cigarette smoke for 12 weeks. The model rats were treated with electroacupuncture (EA) at BL13 and ST36. The lung function and histology of the rats were observed. IL-17, tumor necrosis factor (TNF)-α, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and in plasma. The leukocytes and macrophages in the BALF were counted. The expression levels of IL-17R were assayed in lung tissue by real-time polymerase chain reaction (PCR), western blotting, and immunohistochemistry. MAPK signaling pathway molecules including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)1/2 and p38, and their phosphorylated forms, were observed in the lung by western blotting. Compared with the control group rats, lung function decreased and there was a severe inflammatory infiltration of the pulmonary parenchyma in the COPD rats. EA effectively improved lung function and alleviated the inflammatory infiltration in the lungs of COPD rats. EA also reversed the elevated total leukocyte and macrophage counts, the high levels of IL-17 and TNF-α, and the low IL-10 content in COPD rats. Meanwhile, EA downregulated the increased mRNA and protein expression of IL-17R, and significantly inhibited the elevated levels of phosphorylated JNK, ERK1/2, and p38 in the lungs of COPD rats. Our results suggest that the protective effects of acupuncture therapy on the lungs of COPD rats are likely related to inhibition of IL-17/IL-17R and the post-receptor MAPK signaling pathways.

Post-tuberculosis airway disease: A population-based cohort study of people immigrating to British Columbia, Canada, 1985-2015.

BackgroundCurrent epidemiological evidence of post-TB airway disease is largely cross-sectional and derived from high-TB-incidence settings. We present the first cohort study of post-TB airway disease in a low-TB-incidence setting.Aims(1) analyze the risk of airway disease by respiratory TB, (2) assess potential unmeasured confounding between TB and airway disease, and (3) investigate TB effect measure modification.MethodsA population-based cohort study using healthcare claims data for immigrants to British Columbia (BC), Canada, 1985–2015. Airway disease included chronic airway obstruction, asthma, bronchitis, bronchiolitis, and emphysema. Respiratory TB was defined from TB registry data. Cox proportional hazards (PH) regressions were used to analyze time-to-airway disease by respiratory TB. Sensitivity analyses included varying definitions of TB and airway disease. Potential unmeasured confounding by smoking was evaluated by E-value and hybrid least absolute shrinkage and selection operator (LASSO)-high-dimensional propensity score (hdPS).FindingsIn our cohort (N = 1 005 328; nTB=1141) there were 116 840 incident cases of airway disease during our 30-year study period (10.43 per 1,000 person-years of follow-up), with cumulative incidence of 42·5% among respiratory TB patients compared with 11·6% among non-TB controls. The covariate-adjusted hazard ratio (aHR) for airway disease by respiratory TB was 2·08 (95% CI: 1·91–2·28) with E-value=3·58. The LASSO-hdPS analysis produced aHR=2·26 (95% CI: 2·07–2·47).InterpretationA twofold higher risk of airway disease was observed among immigrants diagnosed with respiratory TB, compared with non-TB controls, in a low-TB-incidence setting. Unmeasured confounding is unlikely to explain this relationship. Models of post-TB care are needed.FundingCanadian Institutes of Health Research.

The use of heated oxygen-helium mixture in patients with chronic obstructive lung disease

BACKGROUND: In recent years, along with the development of new pharmacological approaches and treatment COLD (chronic obstructive lung disease), a significant attention is paid to the study of non-medical methods of treatment and correction of the system inflammation occurring.&#x0D; AIMS: To assess the effectiveness of the use of heated oxygen-helium mixture (OHM) in the rehabilitation of patients with chronic obstructive bronchitis on an outpatient polyclinic stage.&#x0D; MATERIALS AND METHODS: The supervision was 102 patients aged from 32 to 56 (43.74.1) years. All patients entered into research signed voluntary informed consent. Patients were divided into three groups: the first group (n=32) is the control; the second group (n=35) is the main one. Patients of these groups had a verified diagnosis: chronic obstructive bronchitis, moderate and moderate degree of obstruction, the duration of the disease amounted to 2 years to 16 (5.41.4) years. The third group (n=35) is practically healthy patients. The patients of the second and third group passed the respiratory course of heated OHM (the temperature of the mixture in the mask 50). Breathing was carried out in cyclical-fractionated mode: the breath of the mixture 5 minutes then breathing with atmospheric air 5 minutes (one cycle), 3 cycles for the procedure. The course of treatment consisted of 1 procedure per day for 10 days from the first day of the study.&#x0D; The clinical efficacy of reducing treatment was assessed before the start of therapy, after the 10th procedure in the following indicators: Harvard step test index, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (heart rate), blood pressure recovery time, maximum oxygen consumption (MOC); diagnosis of psycho-emotional state using WBAM Questionnaire (well-beingactivitymood).&#x0D; RESULTS: In the group of practically healthy patients, a positive dynamics was noted in the speed of adaptive processes for the restoration of the cardiovascular system after physical exertion of the form of a decrease in blood pressure reduction time, a decrease in systolic blood pressure, the indicators of the Harvard step test index and maximum oxygen consumption increased. Patients with chronic obstructive bronchitis, who passed the breathing rate of heated oxygen-helium mixture, had an increase in points on WBAM Questionnaire, which indicates the improvement of the psycho-emotional state of patients.&#x0D; CONCLUSION: The use of the course of breathing heated oxygen-helium mixture in patients with chronic obstructive bronchitis does not affect the increase in physical performance. The use of heated oxygen-helium mixture has a positive effect on the functional state of practically healthy patients, which is manifested in the form of slowing the connection of the anaerobic mechanisms of energy supply in the process of performing physical exertion, leading to an increase in oxygen consumption, improving physical performance.

Overexpression of FOXA2 attenuates cigarette smoke-induced cellular senescence and lung inflammation through inhibition of the p38 and Erk1/2 MAPK pathways

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible and progressive airflow limitation and encompasses varying degrees of chronic obstructive bronchitis and emphysema. Our previous study showed that Forkhead box protein A2 (FOXA2) is involved in cigarette smoke (CS)-induced squamous metaplasia. However, the contribution of FOXA2 activity to CS-induced cellular senescence and lung inflammation remains largely unknown. Here, we report that FOXA2 was underexpressed in CS-exposed mouse lungs, and decreased expression of FOXA2 was related to cell senescence and inflammation. Subsequent investigation suggested that FOXA2 is an anti-senescence factor in lung that is involved in inflammatory responses. Furthermore, FOXA2 overexpression delayed CSE-induced senescence and inflammation, which correlated with regulation of the p38 and Erk1/2 MAPK signaling pathways by CSE-induced FOXA2 downregulation. Collectivelly, these findings reveal a protective role for FOXA2 as a regulator of cell senescence and inflammation during COPD.