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Background: Bronchial thermoplasty (BT) is a novel endoscopic therapy for severe asthma. Traditionally it is performed in three separate treatment sessions, targeting different portions of the lung, and each requires an anaesthetic and hospital admission. Compression of treatment into 2 sessions would present a more convenient alternative for patients. In this prospective observational study, the safety of compressing BT into two treatment sessions was compared with the traditional 3 treatment approach., Methods: Sixteen patients meeting ERS/ATS criteria for severe asthma consented to participate in an accelerated treatment schedule (ABT), which treated the whole left lung followed by the right lung four weeks later. The short-term outcomes of these patients were compared with 37 patients treated with conventional BT scheduling (CBT). The outcome measures used to assess safety were (1) the requirement to remain in hospital beyond the electively planned 24-h admission and (2) the need for re-admission for any cause within of 30 days of treatment., Results: The total number of radiofrequency activations delivered in the ABT group was similar to CBT (187 ± 21 vs 176 ± 40, p = 0.326). With ABT, 11 in 31 admissions (37.9%) required prolonged admission due to wheezing, compared to 5.4% with CBT (p = 0.0025). The mean hospital length of stay with ABT was 1.8 ± 1.3 days, compared to 1.1 ± 0.4 days (p < 0.001). ICU monitoring was required on 5 occasions with ABT (16.1%), compared to 0.9% with CBT (p = 0.002). Subgroup analysis demonstrated that females were more likely to require prolonged admission (OR 11.6, p = 0.0025). The 30-day hospital readmission rate was similar for both groups (6.4% vs 5.4%, p = 0.67). All patients made a complete recovery after treatment with similar outcomes at the 6-month follow-up reassessment., Conclusion: This study demonstrates that ABT results in greater short-term deterioration in lung function associated with a greater risk of prolonged hospital and ICU stay, predominantly affecting females. Therefore, in females, these risks need to be balanced against the convenience of fewer treatment sessions. In males, it may be an advantage to compress treatment., (© 2021. The Author(s).)

Objectives: Although excitements related to stem cell therapeutic outcomes have been highlighted enormously in asthma, the vast majority of works were conducted by researchers in animal models. Elucidating the mechanisms underlying the therapeutic effects of MSCs in asthmatic rats will provide a rational basis for assuring maximal safety of future clinical application of stem cells. In the current study, we sought to investigate the possible paracrine mechanism by which direct injection of MSCs and/or CM attenuate efficiently Th2-mediated inflammation in asthmatic lung tissues with the focus on ICAM-1 and VCAM-1 expression., Methods: Male rats were divided into four experimental groups (n = 6); healthy rats received PBS intratracheally (group C), sensitized rats received PBS intratracheally (group S), sensitized rats received CM intratracheally (group S + CM), and sensitized rats received PBS intratracheally containing 2 × 10 6 rBMMSCs (group S + MSCs). Two weeks post-transplantation, the expression of interleukin (IL)-5, -12 and INF-γ, ICAM-1 and VCAM-1 were assessed along with pathological injuries and the homing of MSCs into the lung tissues., Results: Our results showed CM, and notably rBMMSCs, returned the expression of IL-5, IL-12, INF-γ, ICAM-1, and VCAM-1 (p < 0.001 to p < 0.05) to the normal levels. Based on data, pathological injuries in pulmonary specimens of asthmatic rats were significantly attenuated (p < 0.001 to p < 0.05). Moreover, rBMMSCs had potential to successfully home to an asthmatic niche in cell-administrated rats., Conclusions: Our data noted the potency of CM and especially MSCs in ameliorating pathological changes via intra-tracheal route presumably by targeting ICAM-1 and VCAM-1 in lung tissues in rat asthma model., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Bronchial thermoplasty (BT) can be considered in the treatment of severe asthma to reduce airway smooth muscle mass and bronchoconstriction. We hypothesized that BT may thus have long-term effects on airway dimensions and air-trapping detectable by quantitative computed tomography (QCT)., Methods: Paired in- and expiratory CT and inspiratory CT were acquired in 17 patients with severe asthma before and up to two years after bronchial thermoplasty and in 11 additional conservatively treated patients with serve asthma, respectively. A fully automatic software calculated the airways metrics for wall thickness (WT), wall percentage (WP), lumen area (LA) and total diameter (TD). Furthermore, lung air-trapping was quantified by determining the quotient of mean lung attenuation in expiration vs. inspiration (E/I MLA) and relative volume change in the Hounsfield interval -950 to -856 in expiration to inspiration (RVC 856-950 ) in a generation- and lobe-based approach, respectively., Results: BT reduced WT for the combined analysis of the 2nd-7th airway generation significantly by 0.06 mm (p = 0.026) and WP by 2.05% (p < 0.001), whereas LA and TD did not change significantly (p = 0.147, p = 0.706). No significant changes were found in the control group. Furthermore, E/I MLA and RVC 856-950 decreased significantly after BT by 12.65% and 1.77% (p < 0.001), respectively., Conclusion: BT significantly reduced airway narrowing and air-trapping in patients with severe asthma. This can be interpreted as direct therapeutic effects caused by a reduction in airway-smooth muscle mass and changes in innervation. A reduction in air-trapping indicates an influence on more peripheral airways not directly treated by the BT procedure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Context: Surgical and pathologic handling of lung physically affects lung tissue. This leads to artifacts that alter the morphologic appearance of pulmonary parenchyma., Objective: To describe and illustrate mechanisms of ex vivo artifacts that may lead to diagnostic pitfalls., Design: In this study 4 mechanisms of ex vivo artifacts and corresponding diagnostic pitfalls are described and illustrated., Results: The 4 patterns of artifacts are: (1) surgical collapse, due to the removal of air and blood from pulmonary resections; (2) ex vivo contraction of bronchial and bronchiolar smooth muscle; (3) clamping edema of open lung biopsies; and (4) spreading of tissue fragments and individual cells through a knife surface. Morphologic pitfalls include diagnostic patterns of adenocarcinoma, asthma, constrictive bronchiolitis, and lymphedema., Conclusion: Four patterns of pulmonary ex vivo artifacts are important to recognize in order to avoid morphologic misinterpretations.

Background: Bronchial thermoplasty (BT) is a bronchoscopic procedure that improves asthma control by reducing excess airway smooth muscle. Treated patients have been followed out to 5 years to evaluate long-term safety of this procedure., Methods: Patients enrolled in the Asthma Intervention Research Trial were on inhaled corticosteroids ≥200 μg beclomethasone or equivalent + long-acting-beta2-agonists and demonstrated worsening of asthma on long-acting-β2-agonist withdrawal. Following initial evaluation at 1 year, subjects were invited to participate in a 4 year safety study. Adverse events (AEs) and spirometry data were used to assess long-term safety out to 5 years post-BT., Results: 45 of 52 treated and 24 of 49 control group subjects participated in long-term follow-up of 5 years and 3 years respectively. The rate of respiratory adverse events (AEs/subject) was stable in years 2 to 5 following BT (1.2, 1.3, 1.2, and 1.1, respectively,). There was no increase in hospitalizations or emergency room visits for respiratory symptoms in Years 2, 3, 4, and 5 compared to Year 1. The FVC and FEV1 values showed no deterioration over the 5 year period in the BT group. Similar results were obtained for the Control group., Conclusions: The absence of clinical complications (based on AE reporting) and the maintenance of stable lung function (no deterioration of FVC and FEV1) over a 5-year period post-BT in this group of patients with moderate to severe asthma support the long-term safety of the procedure out to 5 years.

Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases, including emphysema, pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular reference to animal models., (Copyright 2010 Mosby, Inc. All rights reserved.)

This review examines the rationale for increased study of the prenatal development of airway smooth muscle (ASM). With a critical role in asthma and airway remodelling, ASM has been extensively investigated. Nevertheless, there is a paucity of studies looking at prenatal ASM development and function. A working party report from the National Heart Lung and Blood Institute identified this issue and has recommended further investigation. The impetus for this call stems not only from an appreciation that childhood and adulthood disease may have their origins in fetal life, but also because recent studies indicate that prenatal ASM regulates lung development (via its phasic contractility and growth factor production). Moreover, recognition that phasic ASM contractility is the prenatal norm has raised interest in the idea that postnatal reactive airways disease may likewise be a periodic oscillatory phenomenon. Finally, bronchial thermoplasty represents an exciting new therapy for refractory asthma. However, the mechanism for its effects is unclear. Recent studies show that prenatal ASM contractility is governed by a hierarchy of pacemakers within proximal airways. If such a pacemaker arrangement persists postnatally, it is possible that bronchial thermoplasty achieves its distal airway effects via ablation of controlling proximal pacemaker centres. Hence, study of prenatal ASM may allow us not only to develop ways to stimulate prenatal lung growth, but also to understand and develop new therapies for reactive airways disease.

Selective denervation of the lung (SDL) has been conducted in 389 patients with bronchial asthma. This operation stimulates function of Tg-suppressors, enhances the activity of blocked adrenergic structures and glucocorticoid supply, attenuates adrenal and extraadrenal insufficiency. SDL is thought pathogenetically validated in bronchial asthma with deficient suppression, generalized adrenodeficiency, combined glucocorticoid insufficiency.

The activity of cholino- and adrenoreceptors of blood T-lymphocytes was studied to elaborate the indications for operative interventions various parts of the autonomous nervous system in 117 patients with bronchial asthma. Selective denervation of the root of the lung and glomectomy with denervation of the sinocarotid zone was found to be the most effective type of surgical treatment. The clinical effect of operative treatment is linked with normalization of the activity of cholinoreceptors of blood T-lymphocytes. The high informativeness of the test was demonstrated in predicting the results of operative treatment of patients with bronchial asthma.

Indications for various types of operative intervention in 411 patients (among 986 patients who were examined in a specialized pulmonological department) were determined according to the degree of functional and morphological changes of the respiratory tract by means of complex radiological examination together with other modern methods (radioisotope, immunological, bronchological, etc.) for examination of the bronchopulmonary system in bronchial asthma.