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Background: A disintegrin and metalloproteinase domain-15 (ADAM15) is expressed by activated leukocytes, and fibroblasts in vitro. Whether ADAM15 expression is increased in the lungs of COPD patients is not known.Methods: ADAM15 gene expression and/or protein levels were measured in whole lung and bronchoalveolar lavage (BAL) macrophage samples obtained from COPD patients, smokers, and non-smokers. Soluble ADAM15 protein levels were measured in BAL fluid (BALF) and plasma samples from COPD patients and controls. Cells expressing ADAM15 in the lungs were identified using immunostaining. Staining for ADAM15 in different cells in the lungs was related to forced expiratory volume in 1 s (FEV1), ratio of FEV1 to forced vital capacity (FEV1/FVC), and pack-years of smoking history.Results: ADAM15 gene expression and/or protein levels were increased in alveolar macrophages and whole lung samples from COPD patients versus smokers and non-smokers. Soluble ADAM15 protein levels were similar in BALF and plasma samples from COPD patients and controls. ADAM15 immunostaining was increased in macrophages, CD8+ T cells, epithelial cells, and airway α-smooth muscle (α-SMA)-positive cells in the lungs of COPD patients. ADAM15 immunostaining in macrophages, CD8+ T cells and bronchial (but not alveolar) epithelial cells was related inversely to FEV1 and FEV1/FVC, but not to pack-years of smoking history. ADAM15 staining levels in airway α-SMA-positive cells was directly related to FEV1/FVC. Over-expressing ADAM15 in THP-1 cells reduced their release of matrix metalloproteinases and CCL2.Conclusions: These results link increased ADAM15 expression especially in lung leukocytes and bronchial epithelial cells to the pathogenesis of COPD. [ABSTRACT FROM AUTHOR]

Background: The HHIP gene, encoding Hedgehog interacting protein, has been implicated in chronic obstructive pulmonary disease (COPD) by genome-wide association studies (GWAS), and our subsequent studies identified a functional upstream genetic variant that decreased HHIP transcription. However, little is known about how HHIP contributes to COPD pathogenesis. Methods: We exposed Hhip haploinsufficient mice (Hhip+/-) to cigarette smoke (CS) for 6 months to model the biological consequences caused by CS in human COPD risk-allele carriers at the HHIP locus. Gene expression profiling in murine lungs was performed followed by an integrative network inference analysis, PANDA (Passing Attributes between Networks for Data Assimilation) analysis. Results: We detected more severe airspace enlargement in Hhip+/- mice vs. wild-type littermates (Hhip+/+) exposed to CS. Gene expression profiling in murine lungs suggested enhanced lymphocyte activation pathways in CS-exposed Hhip+/- vs. Hhip+/+ mice, which was supported by increased numbers of lymphoid aggregates and enhanced activation of CD8+ T cells after CS-exposure in the lungs of Hhip+/- mice compared to Hhip+/+ mice. Mechanistically, results from PANDA network analysis suggested a rewired and dampened Klf4 signaling network in Hhip+/- mice after CS exposure. Conclusions: In summary, HHIP haploinsufficiency exaggerated CS-induced airspace enlargement, which models CS-induced emphysema in human smokers carrying COPD risk alleles at the HHIP locus. Network modeling suggested rewired lymphocyte activation signaling circuits in the HHIP haploinsufficiency state. [ABSTRACT FROM AUTHOR]

Background Many asthmatic women complain of symptom exacerbations in particular periods, i.e. during pregnancy and menstrual cycles (perimenstrual asthma: PMA)". The goal of this study was to study the effect of the luteal and follicular phases of the menstrual cycle on bronchial reactivity (BR) in a group of asthmatic women. Methods For this purpose, 36 pre-menopausal women were enrolled and underwent testing for resting pulmonary function, measurement of the diffusing capacity of the lung for carbon monoxide (DLCO), and airway responsiveness to methacholine in the follicular and luteal phases of their menstrual cycles. We also measured plasma hormone levels and levels of cyclicadenosine monophosphate (cAMP; a mediator of bronchial smooth muscle contraction) and testosterone in induced sputum samples. Results Our study showed that about 30% of the asthmatic women had decreased PC20FEV1.0 in the follicular phase of menstrual cycle with a significant correlation between PC20FEV1.0 and serum testosterone levels Moreover, marked increases in sputum testosterone levels (mean = 2.6-fold increase) together with significant increases in sputum cAMP concentrations (mean = 3.6-fold increases) were observed during the luteal phase of asthmatic patients, suggesting that testosterone contributes to the pathophysiology of PMA. We excluded the possibility that testosterone directly inhibits phosphodiesterase (PDE) activity as incubating PDE with testosterone in vitro did not reduce PDE catalytic activity. Conclusions In conclusion, our data show that PC20FEV1.0 was decreased in the follicular phase of the menstrual cycle in about 30% of women and was associated with lower cAMP levels in sputum samples, which may contribute to bronchoconstriction. Our results also suggest a link between PMA and testosterone levels. However, whether these findings are of clinical significance in terms of the management of asthma or asthma worsening during the menstrual cycle needs further investigation. [ABSTRACT FROM AUTHOR]

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool. One of the key promoters of B cell expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly linked to non small cell lung cancer (NSCLC) onset and progression previously. However, little is known about the expression of APRIL in the lungs of COPD patients. Methods: Using immuno-fluorescence staining, the expression of APRIL was assessed in sections of lungs from 4 subjects with primary diagnosis of COPD (FEV1 33 ± 20 % predicted), 4 subjects with primary diagnosis of NSCLC, 4 subjects diagnosed with both COPD and NSCLC, smokers without COPD or NSCLC and 3 healthy never-smokers. The percentage of B cells, alveolar macrophages (AMs) and polymorphonuclear neutrophils (PMNs) in the lung and alveolar epithelial cells (AECs) that stained positively for APRIL was quantified using epi-fluorescence microscopy and image analysis software. Results: The percentage of APRIL-expressing B cells, AMs, PMNs and alveolar epithelial cells (AECs) was higher in patients having both COPD and NSCLC than in patients with either COPD or NSCLC alone, SC or NSC (p < 0.03 for all comparisons). The percentage of APRIL-expressing AMs and AECs (but not in B cells) was higher in patients with NSCLC alone than in patients with COPD alone. The percentage of APRIL-expressing AECs (but not B cells or AMs) was higher in COPD patients than in SC and NSC (p < 0.05 for all comparisons). The percentage of APRIL-expressing B cells, AMs and AECs cells was similar in NSC and SC. Conclusion: The percentage of APRIL-expressing B cells, AMs and AECs is higher in the lungs of patients with both COPD and NSCLC than in patients with COPD or NSCLC alone or control subjects. These findings suggest that APRIL may contribute to the pathogenesis of both COPD and NSCLC, and possibly to the development of NSCLC in patients with established COPD.

This paper summarizes the Part 1 of the proceedings of the 8th International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 1) includes sections regarding: Advances in Asthma and COPD Therapy (Novel Therapeutic Targets for Asthma: Proteinases, Blood Biomarker Changes in COPD Patients); The problem of Hospital Re-Admission following Discharge after the COPD Exacerbation (Characteristics of the Hospitalized COPD Patient, Reducing Hospital Readmissions Following COPD Exacerbation).

This paper summarizes the Part 3 of the proceedings of the 8th International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 3) presents a section regarding Moving Across the Spectrum of Care for Long-Term Ventilation (Moving Across the Spectrum of Care for Long-Term Ventilation, New Indications for Non-Invasive Ventilation, Elective Ventilation in Respiratory Failure - Can you Prevent ICU Care in Patients with COPD?, Weaning in Long-Term Acute Care Hospitals in the United States, The Difficult-to-Wean Patient: Comprehensive management, Telemonitoring in Ventilator-Dependent Patients, Ethics and Palliative Care in Critically-Ill Respiratory Patients, and Ethics and Palliative Care in Ventilator-Dependent Patients).

This paper summarizes the Part 2 of the proceedings of the 8th International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 2) includes sections regarding: Promoting Physical Activity across the Spectrum of COPD (Physical activity: definitions, measurements, and significance; Increasing Physical Activity through Pharmacotherapy in COPD); Pulmonary Rehabilitation in Critical Illness (Complex COPD with comorbidities and its impact during acute exacerbation; Collaborative Self-Management in COPD: A Double-Edged Sword?; and Pulmonary Rehabilitation in Critical Illness.

Idiopathic pulmonary fibrosis (IPF) is defined as a chronic fibrosing interstitial disease of unknown cause, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP); it generally progresses into respiratory failure and death. Although progression of the disease is the most common cause of death, there are increasing reports of its association with other pathologies has been reported: e.g., IPF patients seem more susceptible to cardiovascular diseases. Therefore, other pathologies might also influence the natural course. In this paper, we describe a case of IPF and coronary artery disease (CAD). We emphasize the importance of cardiopulmonary exercise test (CPET) as a useful procedure to monitor disease progression in IPF patients. We also stress the importance of a careful analysis of variables measured for an accurate interpretation of the clinical picture and an improvement of the clinical management of patients. Moreover, we suggest that a careful assessment of CPET parameters may additionally help in the early detection of high cardiovascular ischemic risk.

Acute lung injury is characterized by intense neutrophilic lung inflammation and increased alveolar-capillary barrier permeability leading to severe hypoxemia, and is associated with high mortality despite improvements in supportive care. There is an urgent need for effective therapies for acute lung injury. Zhang and colleagues tested the efficacy of adipose-derived stem cells in acute lung injury in mice. When adipose-derived stem cells were delivered to mice that had been challenged with lipopolysaccharide, they potently limited acute lung inflammation and injury in the mice, indicating that adipose-derived stem cells have therapeutic potential in acute lung injury in humans. Herein, we discuss the advantages and potential limitations of using adipose-derived stem cells as therapeutics for human acute lung injury.