scholarly journals Dysregulation of endocytic machinery and ACE2 in small airways of smokers and COPD patients can augment their susceptibility to SARS-CoV-2 (COVID-19) infections

Author(s):  
Mathew Suji Eapen ◽  
Wenying Lu ◽  
Tillie-Louise Hackett ◽  
Gurpreet K Singhera ◽  
Isobel E. Thompson ◽  
...  

Lungs of smokers and COPD are severely compromised and are susceptible to SARS-CoV-2 attack. The lethal combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication. The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-converting enzyme-2 (ACE2) along with endocytic vacuoles, early endosome antigen-1 (EEA1), late endosome marker RAB7, cathepsin-L and lysosome-associated membrane protein-1 (LAMP-1) as lysosome markers, in the airways of smokers and COPD patients. The study design was cross-sectional and involved lung resections from 39 patients in total, which included 19 patients with GOLD stage I or stage II COPD, of which 9 were current smokers with COPD (COPD-CS), and 10 ex-smokers with COPD (COPD-ES), 10 normal lung function smokers (NLFS) and 10 were never smoking normal controls (NC). Immunostaining for ACE2, EEA1, RAB7, and cathepsin-L was done. A comparative description for ACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups. Further, staining intensity for LAMP-1 lysosomes was measured as the ratio of the LAMP-1 stained areas per total area of epithelium or sub-epithelium, using Image ProPlus software. LAMP-1 expression showed a positive correlation to patient smoking history while in COPD LAMP-1 negatively correlated to lung function. The active presence of ACE2 protein along with endocytic vacuoles such as early/late endosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groups could be more susceptible to COVID-19.

2021 ◽  
pp. 00876-2020
Author(s):  
Mathew Suji Eapen ◽  
Wenying Lu ◽  
Tillie L. Hackett ◽  
Gurpreet Kaur Singhera ◽  
Malik Q. Mahmood ◽  
...  

IntroductionPrevious reports showed epithelial mesenchymal transition (EMT) as an active process that contributes to small airway (SA) fibrotic pathology. Myofibroblasts are highly active pro-fibrotic cells that secrete excessive and altered extracellular matrix (ECM). Here we relate SA myofibroblast presence with airway remodelling, physiology and EMT activity in smokers and COPD patients.MethodsLung resections from non-smoker controls (NC), normal lung function smokers (NLFS), COPD current (CS) and ex-smokers (ES) were stained with anti-human αSMA, collagen 1, and fibronectin. αSMA+ive cells were computed in reticular basement membrane (Rbm), lamina propria (LP), and adventitia and presented per mm of Rbm and mm2 of LP. Collagen-1 and fibronectin are presented as a percentage change from normal. All analysis including airway thickness were measured using Image-pro-plus 7.0.ResultsWe found an increase in sub-epithelial LP (especially) and adventitia thickness in all pathological groups compared to NC. Increases in αSMA+ive myofibroblasts were observed in sub-epithelial Rbm, LP, and adventitia in both the smoker and COPD groups compared to NCs. Further, the increase in the myofibroblast population in the LP was strongly associated with decrease in lung function, LP thickening, increase in ECM protein deposition, and finally EMT activity in epithelial cells.ConclusionsThis is the first systematic characterisation of small airway myofibroblasts in COPD based on their localisation, with statistically significant correlations between them and other pan-airway structural, lung function, and ECM protein changes. Finally, we suggest that EMT may be involved in such changes.


Thorax ◽  
2018 ◽  
Vol 73 (6) ◽  
pp. 538-545 ◽  
Author(s):  
Sandra Ekström ◽  
Jenny Hallberg ◽  
Inger Kull ◽  
Jennifer L P Protudjer ◽  
Per Thunqvist ◽  
...  

BackgroundFew large prospective studies have investigated the impact of body mass index (BMI) on lung function during childhood.MethodsUsing data collected between 2002 and 2013, we analysed associations between BMI status and lung function (assessed by spirometry) from 8 to 16 years, as well as cross-sectional associations with small airway function (impulse oscillometry) at 16 years in the BAMSE cohort (n=2889). At 16 years, cross-sectional associations with local and systemic inflammation were investigated by analysing FENO, blood eosinophils and neutrophils.ResultsOverweight and obesity at 8 years were associated with higher FVC, but lower FEV1/FVC ratio at 8 and 16 years. In boys, but not girls, obesity at 8 years was associated with a further reduction in FEV1/FVC between 8 and 16 years. In cross-sectional analyses, overweight and obesity were associated with higher frequency dependence of resistance (R5–20) and larger area under the reactance curve (AX0.5) at 16 years. Increased blood neutrophil counts were seen in overweight and obese girls, but not in boys. No association was found between BMI status and FENO. Persistent, but not transient, overweight/obesity between 8 and 16 years was associated with higher R5–20 and AX0.5 and lower FEV1/FVC (−2.8% (95% CI −4.1 to −1.2) in girls and −2.7% (95% CI −4.4 to −1.1) in boys) at 16 years, compared with persistent normal weight.ConclusionIn childhood and adolescence, overweight and obesity, particularly persistent overweight, were associated with evidence of airway obstruction, including the small airways.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dimitrios Kalafatis ◽  
Jing Gao ◽  
Ida Pesonen ◽  
Lisa Carlson ◽  
C. Magnus Sköld ◽  
...  

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a disease with poor prognosis mainly affecting males. Differences in clinical presentation between genders may be important both for the diagnostic work-up and for follow-up. In the present study, we therefore explored potential gender differences at presentation in a Swedish cohort of IPF-patients. Methods We studied patients included in the Swedish IPF- registry over a three-year period from its launch in 2014. A cross-sectional analysis was performed for data concerning demographics, lung function, 6- min walking test (6MWT) and quality of life (QoL) (King’s Brief Interstitial Lung Disease (K-BILD) score). Results Three hundred forty- eight patients (250 (72%) males, 98 (28%) females, median age 72 years in both genders) were included in the registry during the study period. Smoking history (N = 169 (68%) vs. N = 53 (54%), p < 0.05), baseline lung function (Forced vital capacity, % of predicted (FVC%): 68.9% ± 14.4 vs. 73.0% ± 17.7, p < 0.05; Total lung capacity, % of predicted (TLC%): 62.2% ± 11.8 vs. 68.6% ± 11.3%, p < 0.001) were significantly different at presentation between males and females, respectively. Comorbidities such as coronary artery disease (OR: 3.5–95% CI: 1.6–7.6) and other cardiovascular diseases (including atrial fibrillation and heart failure) (OR: 3.8–95% CI: 1.9–7.8) also showed significant differences between the genders. The K- BILD showed poor quality of life, but no difference was found between genders in total score (54 ± 11 vs. 54 ± 10, p = 0.61 in males vs. females, respectively). Conclusions This study shows that female patients with IPF have a more preserved lung function than males at inclusion, while males have a significant burden of cardiovascular comorbidities. However, QoL and results on the 6MWT did not differ between the groups. These gender differences may be of importance both at diagnosis and follow- up of patients with IPF.


1970 ◽  
Vol 6 (2) ◽  
pp. 22-30 ◽  
Author(s):  
R Shrestha ◽  
R Shakya

Introduction : Chronic Obstructive Pulmonary Disease (COPD) is one of the leading problems affecting majority of population all over the world which diminishes the quality of life of the individual and create extra burden to the society as well as country. Inhaled bronchodilator therapy is the mainstay of treatment in the management of COPD. Various inhaled [e.g. metered dose inhaler (MDI) /dry powder inhaler (DPI)] formulations are available and are widely used among the COPD patients in Nepal. Methodology : This is cross sectional prospective study, designed to compare the bronchodilating effect produced when salbutamol is delivered via two devices: MDI (Asthalin® from Cipla) and DPI (Asthalin® rotacap delivered via Rotahaler® from Cipla), in patients with stable COPD. It is proven by previous studies that intervention is necessary to improve the compliance of the patients; all subjects (total n=60; 30 in each group) are counseled and trained to follow correct inhaling technique through particular device. Then their improvements in lung function were measured with reference to the pulmonary function test based on spirometry. Results : Patients enrolled in each group were not statistically different regarding to age (P=0.318), weight (P=0.324) & BMI (P=0.836). Among the total subjects 87% had smoking history and 2% were still smoking and there was no signifi cant difference in smoking habit between the two groups (p-value 0.544 > 0.05). Similarly 91.6 % of the total had exposure to indoor air pollution which had been the major risk factor for COPD. Most of the patients were on stage II COPD (62%). Salbutamol was found to have no effect on vital statistics of patients. Study showed there was no significant difference in the improvement of forced expiratory volume in one second (FEV1) (p=0.802), FVC (p= 0.693), FEV1 % (p=1) and PEF (p=0.448) between MDI and Rotahaler groups. Major side effect associated with the MDI users is headache (79%) while those among Rotahaler users were muscle cramps (79%). Even though intervention improved the inhaler using technique among the patients in both the groups, it was found even after counseling, DPI seemed to be better understood by the patients in comparison to MDI (p=0.003 & 0.00). In addition DPI was preferred by most of the patients who were familiar with both delivery systems. It was also found to be cheaper than the MDI. Conclusion : Overall evidence suggests that although both MDI & DPI improve the lung function of COPD patients to similar extent, DPI is cheaper and more preferred and can be easily handled by the patients which can result in reduction of non-compliance. Keyword : COPD; Salbutamol; DPI; MDI; Spirometry DOI: 10.3126/saarctb.v6i2.3054 SAARC J. Tuber. Lung Dis. HIV/AIDS 2009 VI (2) 22-30


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sarah E. Van Riel ◽  
Kerstin Klipstein-Grobusch ◽  
Roos E. Barth ◽  
Diederick E. Grobbee ◽  
Charles Feldman ◽  
...  

Background: Studies have associated HIV with an increased risk of obstructive lung disease (OLD).Objectives: We aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population.Method: A cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of 0.70, or below the 20th percentile of normal.Results: The 98 ART-naïve participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (β = –0.003, P 0.01), male sex (β = –0.016, P = 0.03) and history of TB or pneumonia (β = –0.024, P 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47–4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64).Conclusion: Our data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia.


2020 ◽  
Vol 8 (B) ◽  
pp. 709-715
Author(s):  
Ni Luh Putu Eka Arisanti ◽  
Ni Putu Ayu Widiasari ◽  
Ida Bagus Ngurah Rai

AIM: The objective of the study was to determine chronic respiratory symptoms and lung function of farmers. METHODS: The study was conducted in Utu Village, Tabanan, Bali with 84 subjects. This research was observational analytic cross sectional study. RESULTS: Three dominant chronic respiratory symptoms in farmers were coughing (15.1%), dyspnea (13.1%), and phlegm (13.1%). Average values of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC were 83.75 ± 34.42, respectively, 81.62 ± 34.30 and 104.90 ± 13.90, respectively. Cough was dominant experiencing by smokers (p = 0.008). Mean of FEV1% prediction and FVC% prediction value was lower in passive smoker group than no smoker group (p = 0.005 and p = 0.03). CONCLUSION: Occupational exposure while farming and raising livestock can cause chronic respiratory symptom and lung function decline in farmers and can be influenced by smoking history and secondhand smoke exposure.


2018 ◽  
Vol 4 (4) ◽  
pp. 00080-2018 ◽  
Author(s):  
David I. Fielding ◽  
Justin Travers ◽  
Phan Nguyen ◽  
Michael G. Brown ◽  
Gunter Hartel ◽  
...  

Expiratory dynamic airways collapse (EDAC) is a condition that affects the central airways; it is not well characterised physiologically, with relatively few studies. We sought to characterise impulse oscillometry (IOS) features of EDAC in patients with normal spirometry. Expiratory data were hypothesised to be the most revealing. In addition, we compared IOS findings in chronic obstructive pulmonary disease (COPD) patients with and without EDAC.EDAC was identified at bronchoscopy as 75–100% expiratory closure at the carina or bilateral main bronchi. Four patient groups were compared: controls with no EDAC and normal lung function; lone EDAC with normal lung function; COPD-only patients; and COPD patients with EDAC.38 patients were studied. Mean IOS data z-scores for EDAC compared to controls showed significantly higher reactance (X) values including X at 5 Hz, resonance frequency and area under the reactance curve (AX). EDAC showed significantly greater expiratory/inspiratory differences in all IOS data compared to controls. Stepwise logistic regression showed that resonant frequency best discriminated between EDAC and normal control, whereas classification and regression tree analysis found AX ≥3.523 to be highly predictive for EDAC in cases with normal lung function (14 out of 15 cases, and none out of eight controls).These data show a new utility of IOS: detecting EDAC in patients with normal lung function.


BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e023450
Author(s):  
Kentaro Watai ◽  
Kiyoshi Sekiya ◽  
Hiroaki Hayashi ◽  
Yuma Fukutomi ◽  
Masami Taniguchi

ObjectiveIn daily clinical practice, smokers with asthma and with intermittent disease severity are frequently encountered. The effects of short-term smoking on lung function or disease presentation in younger patients with intermittent adult-onset asthma remain unclear. We sought to clarify the effects of short-term smoking (<10 pack-years) on lung function and airway hyper-responsiveness (AHR) in young patients with untreated intermittent adult-onset asthma.DesignRetrospective, cross-sectional study.SettingA single primary–tertiary medical centre in Japan.ParticipantsFrom patients who underwent bronchodilator reversibility tests between January 2004 and March 2011 (n=7291), 262 consecutive patients (age, 20–34 years) with untreated intermittent adult-onset asthma, including 157 never smokers and 105 current smokers within 10 pack-years, were analysed.Primary and secondary outcome measuresThe primary outcome was the association of the daily smoking frequency (number of cigarettes per day), smoking duration (years) and cumulative smoking history (pack-years) with postbronchodilator lung function. The secondary outcome was the association of the former three smoking parameters with AHR.ResultsThe daily smoking frequency, smoking duration and cumulative smoking history were significantly associated with decreased postbronchodilator lung function. Daily smoking of ≥11 cigarettes per day was also associated with marked AHR (OR 2.23; 95% CI 1.03 to 4.80), even after adjustment for age, sex, disease duration and body mass index.ConclusionShort-term active smoking in early adulthood may be associated with decreased lung function and AHR, even in patients with intermittent adult-onset asthma. Our findings suggest a benefit of never smoking, even for young patients with intermittent adult-onset asthma.


2001 ◽  
Vol 57 (4) ◽  
pp. 29
Author(s):  
M. Papadopoulos ◽  
I. Muller ◽  
S. Cullen

Background: Urinary incontinence has been experienced as a problem since 1500 BC. In the twentieth century it is still a major problem that remains a source of distress for many sufferers. A lack of literature regarding the prevalence  of stress urinary incontinence (SUI) amongst chronic obstructive pulmonary disease (COPD) patients lead to this studyObjective: To determine the prevalence of stress urinary incontinence in female COPD patients between the ages of 30 and 70 years.Methods: This cross-sectional study included 67 female COPD patients (aged 30-70 years) who were interviewed during a three month period. A structured COPD / incontinence questionnaire was used to obtain data. Statistical analysis of results included Fisher’s exact test and two-tailed t-tests. A p-value of < 0,05 was considered to be statistical significant.Results: The prevalence of SUI in female COPD patients was estimated as 82,1%. Smoking history was the only variable with a significant positive correlation regarding the patients presenting with SUI (p < 0,05). The proportion of smokers in the subjects presenting with SUI (SUI group - 29/55) is significantly higher than the subjects with no symptoms of SUI (normal group - 2/12).Discussion and Conclusion: The outcome of this study revealed a high prevalence of SUI in female COPD patients. Cigarette smoking, as the major contributing factor, revealed a strong statistical correlation between COPD and SUI.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tao Yang ◽  
Chihua Chen ◽  
Zhongyuanlong Chen

Abstract Background It is necessary to analyze the CT pulmonary vascular parameters and disease severity in chronic obstructive pulmonary disease (COPD) patients to provide evidence support for the management of COPD. Methods COPD patients on acute exacerbation admitted to our hospital from COPD patients from January 2019 to March 2020 was selected. The characteristics and ratio of the cross-sectional area (CSA) of small pulmonary vessels to the total area of the lung field, and the ratio of pulmonary artery and aorta (PA/A) cross-sectional diameter in patients with COPD were analyzed. Results A total of 128 COPD patients were included. There were significant differences in the duration of COPD, smoking history, the PaO2, PaCO2, pH, and FEV1, FVC and FEV1/FVC among COPD patients with different severity (all p < 0.05). The duration of COPD, smoking, PaO2, PaCO2, CSA and PA/A were correlated with the COPD severity (all p < 0.05). Both CSA, PA/A were correlated with post BD FEV1 (all p < 0.05). The cutoff value of CSA and PA/A for the diagnosis of severe COPD was 0.61 and 0.87 respectively, and the AUC of CSA and PA/A for the diagnosis of severe COPD was 0.724 and 0.782 respectively. Conclusions Patients with CSA ≤ 0.61 and PA/A ≥ 0.87 may have higher risks for severe COPD, and more studies are needed in the future to further elucidate the management of COPD.


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