Background/aims Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. This study aimed to identify overlapping or diverging dysregulated genes, lncRNAs, miRNAs and signaling pathways in smoking and non-smoking chronic obstructive pulmonary disease (COPD). Methods Compared to normal controls, we identified the shared and divergent differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in smoking and non-smoking COPD by RNA-sequencing and bioinformatics analysis. Functional annotation of DEmRNAs were performed. Both cis and trans-target DEmRNAs of DElncRNAs were identified. The target DEmRNAs of DEmiRNAs were identified as well. The DEmiRNA-DEmRNA-DElncRNA interaction network was constructed. QRT-PCR was performed to validat the selected DEmiRNAs, DEmRNA and DElncRNAs in COPD. Results Compared to normal control, 1234 DEmRNAs, 96 DElncRNAs and 151 DEmiRNAs were identified in non-smoking patients with COPD; 670 DEmRNAs, 44 DElncRNAs and 63 DEmiRNAs were identified in smoking patients with COPD. Leukocyte transendothelial migration and pathways in cancer were significantly enriched pathways in non-smoking and smoking COPD, respectively. MiR-122-5p-A2M-LINC00987/A2M-AS1/ linc0061 interactions might play key roles in COPD irrespective with the smoking status. Let-7-ADRB1-HLA-DQB1-AS1 might play a key role in the pathogenesis of smoking COPD while miR-218-5p/miR15a-RORA-LOC101928100/LINC00861 and miR-218-5p/miR15a-TGFβ3-RORA-AS1 interactions might involve with non-smoking COPD. Conclusion We identified the shared and diverging genes, lncRNAs, miRNAs and their interactions and pathways in smoking and non-smoking COPD which provided clues for understanding the mechanism and developing novel diagnostic and therapeutic strategies for COPD.

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Comprehensive Analysis of miRNA-mRNA-lncRNA Networks in Non-Smoking and Smoking Patients with Chronic Obstructive Pulmonary Disease.

The nervous system mediates key airway protective behaviors, including cough, mucus secretion, and airway smooth muscle contraction. Thus, its involvement and potential involvement in several airway diseases has become increasingly recognized. In the current review, we focus on the contribution of select neuropeptides in three distinct airway diseases: asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. We present data on some well-studied neuropeptides, as well as call attention to a few that have not received much consideration. Because mucus hypersecretion and mucus obstruction are common features of many airway diseases, we place special emphasis on the contribution of neuropeptides to mucus secretion. Finally, we highlight evidence implicating involvement of neuropeptides in mucus phenotypes in asthma, COPD and cystic fibrosis, as well as bring to light knowledge that is still lacking in the field.

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Neuropeptides in asthma, chronic obstructive pulmonary disease and cystic fibrosis.

Exposure to particulate matter (PM) is leading to various respiratory health outcomes. Compared to coarse and fine particles, less is known about the effects of chronic exposure to ultrafine particles, despite their higher number and reactivity. In the present study, we performed a time-course experiment in mice to better analyze the lung impact of atmospheric ultrafine particles, with regard to the effects induced by fine particles collected on the same site. Trace element and PAH analysis demonstrated the almost similar chemical composition of both particle fractions. Mice were exposed intranasally to FF or UFP according to acute (10, 50 or 100 µg of PM) and repeated (10 µg of PM 3 times a week during 1 or 3 months) exposure protocols. More particle-laden macrophages and even greater chronic inflammation were observed in the UFP-exposed mice lungs. Histological analyses revealed that about 50% of lung tissues were damaged in mice exposed to UFP for three months versus only 35% in FF-exposed mice. These injuries were characterized by alveolar wall thickening, macrophage infiltrations, and cystic lesions. Taken together, these results strongly motivate the update of current regulations regarding ambient PM concentrations to include UFP and limit their emission.

https://www.mdpi.com/1660-4601/16/7/1210/pdf

Exposure to Atmospheric Ultrafine Particles Induces Severe Lung Inflammatory Response and Tissue Remodeling in Mice.

Chronic obstructive pulmonary disease (COPD) can be associated with systemic inflammatory trademarks and can coexist with other chronic debilitating diseases such as osteoporosis, which is considered among the most serious comorbidities of COPD. In this review, we aimed at finding answers for the following questions and tried to encapsulate the available literature: (1) how prevalent is osteoporosis among patients with COPD? (2) What are severity patterns of osteoporosis in case of COPD? (3) What are the therapeutic outcomes for patients with osteoporotic COPD? The total number of patients with COPD from all studies was 3815, majority of which were male (2658) representing 69.67% of patients. The mean ± standard deviation for percentage of forced expiratory volume in 1s (FEV1%) was 55.43 ± 14.62%, body mass index for almost 91.29% of patients was 24.4 ± 4.45 kg/m2, whereas fat-free mass index (FFMI) was 17 ± 0.93 kg/m2 for 17.66%. The percentage of patients with COPD having osteoporosis varied in the analyzed studies from 14% up to 66.6%. The mean prevalence of reported osteopenia from 14 studies (n = 2107) was 39.91%, whereas for osteoporosis, the mean prevalence was 37.62% for all included studies. Osteoporosis was highly prevalent among patients with COPD. It is reasonable to call for osteoporosis screening in patients with COPD who are above 65 years, in advanced stages, with BMI lower than 21 kg/m2 or with FFMI lower than 16 kg/m2 for males and 15 kg/m2 for females. There is a lack of research investigating severity and treatments of osteoporosis in patients with COPD.

Osteoporosis among Patients with Chronic Obstructive Pulmonary Disease: Systematic Review and Meta-analysis of Prevalence, Severity, and Therapeutic Outcomes.

Purpose
To report a rare case of encephalocraniocutaneous lipomatosis (ECCL) presented with characteristic multiple organ involvement.

Encephalocraniocutaneous lipomatosis (Fishman syndrome): A rare neurocutaneous syndrome

Background To evaluate the role of HRCT in quantifying emphysema in severe COPD patients and to study the variations in the pattern of emphysema in relation to age, sex, FEV1, smoking index, biomass exposure, and BMI. Material/methods Automatic lung segmentation of HRCT scans in 41 severe COPD patients (GOLD stage III or more) was done using an emphysema protocol. The extent of emphysema was assessed using the density mask method with a threshold of -950 HU (%LAA-950). The percentage of emphysema in each lung lobe and both lungs was correlated with 6 parameters - age, sex, BMI, smoking index, biomass exposure, and FEV1. Results Smoking resulted in homogenously distributed emphysema regardless of the severity of smoking. BMI was inversely correlated with the extent of emphysema. A significant association was found between the percentage of emphysema in the right lower lobe and BMI (P=0.015), between biomass exposure and the percentage of emphysema in RUL, RLL, and both lungs (P values of 0.024, 0.016, and 0.036, respectively). The extent of emphysema was disproportionately low compared to the amount of obstruction on PFTs, indicating an airway predominant variety of COPD with significant biomass exposure. Conclusions Smoking is associated with a relatively homogenous distribution of emphysema with no regional predilection. Biomass exposure produces predominantly right-sided emphysema. BMI decreases with increasing levels of emphysema in the right lower lobe. These risk factors of emphysema patterns are helpful in deciding on the management, including surgical options.

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Quantitative Computed Tomography (CT) Assessment of Emphysema in Patients with Severe Chronic Obstructive Pulmonary Disease (COPD) and its Correlation with Age, Sex, Pulmonary Function Tests, BMI, Smoking, and Biomass Exposure.

Encephalocraniocutaneous lipomatosis (ECCL), also known as Haberland syndrome, is a rare syndrome with unknown etiology. The syndrome is characterized by a triad of unique cutaneous, ocular, and central nervous system (CNS) manifestations. The cutaneous hallmark, nevus psiloliparus (NP), along with overlying alopecia is a constant feature. Choristoma of the eyelid is the most common ocular manifestation, while intracranial lipoma is the predominant CNS finding. Genetic counseling is required to emphasize that the disorder, although congenital, is not inheritable. We present a 21-year-old female with cutaneous, ocular, and CNS features satisfying the diagnostic criteria for ECCL. To our knowledge, this is the first case of ECCL having a large temporal exostosis. The objective of this article is to better understand the phenotypic spectrum of this syndrome whose molecular basis is still unknown.

Encephalocraniocutaneous lipomatosis with calvarial exostosis - Case report and review of literature

Background: Chronic obstructive pulmonary disease (COPD) is a lifestyle-related chronic inflammatory pulmonary disease and a major cause of morbidity and mortality globally. Osteoporosis and osteopenia are common observations in COPD and degree of the loss of bone mineral density (BMD) has been found to be proportionate to the severity of the disease. Objectives: Our objective was to study the prevalence of osteoporosis and osteopenia in stable COPD patients in Indian Sub-Himalayan population. Materials and Methods: This study was performed on 84 patients of COPD attending as outpatient in the Pulmonary Medicine Department after application of inclusion and exclusion criteria. A control group of 60 healthy controls was selected for comparison with COPD group. Spirometry was done on patients to stage the severity of COPD according to global initiative for chronic obstructive lung disease criteria. Dual-energy X-ray absorptiometry scan of the lumbar spine was done using bone densitometer to determine the severity of reduced BMD. The patients were categorized according to the World Health Organization criterion for definition of reduced BMD. Results: In the present study, a total of 45.2% patients had osteoporosis, 41.6% patients had osteopenia while the rest 13% patients had normal bone density in the COPD group. The prevalence of low bone density was about 4 times higher in COPD group as compared to control group. There were 15.48 times higher chances of low BMD in COPD patients as compared to healthy controls. Conclusions: Reduced BMD is a common comorbid entity in COPD patients which leads to increase in bone fragility and susceptibility to fracture. It is recommended that all the patients with COPD should be screened for osteoporosis to initiate the treatment for the disorder before they develop fractures.

Prevalence of osteoporosis and osteopenia in stable patients of chronic obstructive pulmonary disease in Sub-Himalayan region of Himachal Pradesh, India

Vijay Thakur

Papers

Quantitative Computed Tomography (CT) Assessment of Emphysema in Patients with Severe Chronic Obstructive Pulmonary Disease (COPD) and its Correlation with Age, Sex, Pulmonary Function Tests, BMI, Smoking, and Biomass Exposure.

Encephalocraniocutaneous lipomatosis with calvarial exostosis - Case report and review of literature

Prevalence of osteoporosis and osteopenia in stable patients of chronic obstructive pulmonary disease in Sub-Himalayan region of Himachal Pradesh, India