Nanoparticle diffusion in spontaneously expectorated sputum as a biophysical tool to probe disease severity in COPD

Perturbations in airway mucus properties contribute to lung function decline in patients with chronic obstructive pulmonary disease (COPD). While alterations in bulk mucus rheology have been widely explored, microscopic mucus properties that directly impact on the dynamics of microorganisms and immune cells in the COPD lungs are yet to be investigated.We hypothesised that a tightened mesh structure of spontaneously expectorated mucus (i.e. sputum) would contribute to increased COPD disease severity. Here, we investigated whether the mesh size of COPD sputum, quantified by muco-inert nanoparticle (MIP) diffusion, correlated with sputum composition and lung function measurements.The microstructure of COPD sputum was assessed based on the mean squared displacement (MSD) of variously sized MIPs measured by multiple particle tracking. MSD values were correlated with sputum composition and spirometry. In total, 33 samples collected from COPD or non-COPD individuals were analysed.We found that 100 nm MIPs differentiated microstructural features of COPD sputum. The mobility of MIPs was more hindered in sputum samples from patients with severe COPD, suggesting a tighter mucus mesh size. Specifically, MSD values inversely correlated with lung function.These findings suggest that sputum microstructure may serve as a novel risk factor for COPD progression and severity.

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RISK FACTORS OF INCREASING LUNG FUNCTION DECLINE IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A REAL-WORLD ANALYSIS

Respirology ◽

10.1111/resp.13207_425 ◽

2017 ◽

Vol 22 ◽

pp. 248-248

Keyword(s):

Risk Factors ◽

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Pulmonary Disease ◽

Real World ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease

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Association of Plasma Heat Shock Protein 70 with Disease Severity, Smoking and Lung Function of Patients with Chronic Obstructive Pulmonary Disease

10.21203/rs.3.rs-41671/v1 ◽

2020 ◽

Author(s):

Iva Hlapčić ◽

Andrea Hulina-Tomašković ◽

Marija Grdić Rajković ◽

Sanja Popović-Grle ◽

Andrea Vukić Dugac ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Heat Shock ◽

Lung Function ◽

Heat Shock Protein ◽

Disease Severity ◽

Heat Shock Protein 70 ◽

Smoking Status ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients

Abstract Background: Extracellular heat shock protein 70 (eHsp70) acts like a damage-associated molecular pattern (DAMP) and it might modulate immune responses in patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore plasma eHsp70 concentration in patients with stable COPD, its association with disease severity and smoking status as well as its diagnostic performance in COPD assessment.Methods: Blood samples were collected from 137 COPD patients and 95 healthy individuals. COPD patients were subdivided into GOLD 2-4 stages based on airflow obstruction severity and GOLD A-D groups regarding symptoms and exacerbations. Concentration of eHsp70 was assessed in EDTA plasma by the commercially available ELISA kit. Statistic analysis was performed by MedCalc statistical software.Results: eHsp70 concentration was increased in COPD patients when compared to controls and was increasing with the severity of airflow limitation as well as symptoms burden and exacerbation history. There were no differences in eHsp70 concentrations among COPD patients based on smoking status, yet eHsp70 was increased in healthy smokers compared to healthy non-smokers. Interestingly, healthy smokers had similar eHsp70 level as COPD patients in GOLD 2 stage and those in GOLD A group. In addition, eHsp70 showed significant negative correlation with lung function parameters FEV1 and FEV1/FVC and positive correlation with COPD multicomponent indices BODCAT, BODEx, CODEx and DOSE. Finally, eHsp70 showed great predictive value (OR=7.63) and correctly classified 76% of cases.Conclusions: Plasma eHsp70 is associated with COPD prediction and disease severity and might have a potential of becoming an additional biomarker in COPD assessment.

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Computed tomography-derived area and density of pectoralis muscle associated disease severity and longitudinal changes in chronic obstructive pulmonary disease: a case control study

Respiratory Research ◽

10.1186/s12931-019-1191-y ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 5

Author(s):

So Hyeon Bak ◽

Sung Ok Kwon ◽

Seon-Sook Han ◽

Woo Jin Kim

Keyword(s):

Computed Tomography ◽

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Pulmonary Function ◽

Pulmonary Disease ◽

Disease Severity ◽

Chronic Obstructive ◽

Pectoralis Muscle ◽

Obstructive Pulmonary Disease ◽

Longitudinal Changes

Abstract Background Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). The cross-sectional area of skeletal muscles on computed tomography (CT) could serve as a method to evaluate body composition. The present study aimed to determine the ability of CT-derived pectoralis muscle area (PMA) and pectoralis muscle density (PMD) to determine the severity of COPD and change in longitudinal pulmonary function in patients with COPD. Methods A total of 293 participants were enrolled in this study, a whom 222 had undergone at least two spirometry measurements within 3 years after baseline data acquisition. PMA and PMD were measured from a single axial slice of chest CT above the aortic arch at baseline. The emphysema index and bronchial wall thickness were quantitatively assessed in all scans. The generalized linear model was used to determine the correlation between PMA and PMD measurements and pulmonary function. Results PMA and PMD were significantly associated with baseline lung function and the severity of emphysema (P < 0.05). Patients with the lowest PMA and PMD exhibited significantly more severe airflow obstruction (β = − 0.06; 95% confidence interval: − 0.09 to − 0.03]. PMA was statistically associated with COPD assessment test (CAT) score (P = 0.033). However, PMD did not exhibit statistically significant correlation with either CAT scores or modified Medical Research Council scores (P > 0.05). Furthermore, neither PMA nor PMD were associated with changes in forced expiratory volume in 1 s over a 3-year periods. Conclusions CT-derived features of the pectoralis muscle may be helpful in predicting disease severity in patients with COPD, but are not necessarily associated with longitudinal changes in lung function.

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Lung function, forced expiratory volume in 1 s decline and COPD hospitalisations over 44 years of follow-up

European Respiratory Journal ◽

10.1183/13993003.01575-2015 ◽

2015 ◽

Vol 47 (3) ◽

pp. 742-750 ◽

Cited By ~ 8

Author(s):

Suneela Zaigham ◽

Per Wollmer ◽

Gunnar Engström

Keyword(s):

Lung Function ◽

Airflow Obstruction ◽

Fixed Ratio ◽

Population Based ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Hazard Ratios

The use of baseline lung function in the prediction of chronic obstructive pulmonary disease (COPD) hospitalisations, all-cause mortality and lung function decline was assessed in the population-based “Men Born in 1914” cohort.Spirometry was assessed at age 55 years in 689 subjects, of whom 392 had spirometry reassessed at age 68 years. The cohort was divided into three groups using fixed ratio (FR) and lower limit of normal (LLN) criterion: forced expiratory volume in 1 s (FEV1)/vital capacity (VC) ≥70%, FEV1/VC <70% but ≥LLN (FR+LLN−), and FEV1/VC <70% and <LLN (FR+LLN+).Over 44 years of follow-up, 88 men were hospitalised due to COPD and 686 died. Hazard ratios (95% CI) for incident COPD hospitalisation were 4.15 (2.24–7.69) for FR+LLN− and 7.88 (4.82–12.87) for FR+LLN+ (reference FEV1/VC ≥70%). Hazard ratios for death were 1.30 (0.98–1.72) for FR+LLN− and 1.58 (1.25–2.00) for FR+LLN+. The adjusted FEV1 decline between 55 and 68 years of age was higher for FR+LLN− and FR+LLN+ relative to the reference. Of those with FR+LLN− at 55 years, 53% had progressed to the FR+LLN+ group at 68 years.Airflow obstruction at age 55 years is a powerful risk factor for future COPD hospitalisations. The FR+LLN− group should be carefully evaluated in clinical practice in relation to future risks and potential benefit from early intervention. This is reinforced by the increased FEV1 decline in this group.

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Global Initiative for Chronic Obstructive Lung Disease 2017 Classification and Lung Function Decline in Chronic Obstructive Pulmonary Disease

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201706-1154le ◽

2018 ◽

Vol 197 (5) ◽

pp. 670-673 ◽

Cited By ~ 11

Author(s):

Wan C. Tan ◽

Jean Bourbeau ◽

Shawn D. Aaron ◽

Guohai Zhou ◽

Francois Maltais ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Lung Disease ◽

Pulmonary Disease ◽

Obstructive Lung Disease ◽

Chronic Obstructive Lung Disease ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Global Initiative

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BMI is associated with FEV1 decline in chronic obstructive pulmonary disease: a meta-analysis of clinical trials

Respiratory Research ◽

10.1186/s12931-019-1209-5 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 16

Author(s):

Yilan Sun ◽

Stephen Milne ◽

Jen Erh Jaw ◽

Chen Xi Yang ◽

Feng Xu ◽

...

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Clinical Trials ◽

Lung Function ◽

Protective Effect ◽

Obesity Paradox ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Meta Regression ◽

The Relationship

Abstract Background There is considerable heterogeneity in the rate of lung function decline in chronic obstructive pulmonary disease (COPD), the determinants of which are largely unknown. Observational studies in COPD indicate that low body mass index (BMI) is associated with worse outcomes, and overweight/obesity has a protective effect – the so-called “obesity paradox”. We aimed to determine the relationship between BMI and the rate of FEV1 decline in data from published clinical trials in COPD. Methods We performed a systematic review of the literature, and identified 5 randomized controlled trials reporting the association between BMI and FEV1 decline. Four of these were included in the meta-analyses. We analyzed BMI in 4 categories: BMI-I (< 18.5 or < 20 kg/m2), BMI-II (18.5 or 20 to < 25 kg/m2), BMI-III (25 to < 29 or < 30 kg/m2) and BMI-IV (≥29 or ≥ 30 kg/m2). We then performed a meta-regression of all the estimates against the BMI category. Results The estimated rate of FEV1 decline decreased with increasing BMI. Meta-regression of the estimates showed that BMI was significantly associated with the rate of FEV1 decline (linear trend p = 1.21 × 10− 5). Conclusions These novel findings support the obesity paradox in COPD: compared to normal BMI, low BMI is a risk factor for accelerated lung function decline, whilst high BMI has a protective effect. The relationship may be due to common but as-of-yet unknown causative factors; further investigation into which may reveal novel endotypes or targets for therapeutic intervention.

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Role of Diet in Chronic Obstructive Pulmonary Disease Prevention and Treatment

Nutrients ◽

10.3390/nu11061357 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1357 ◽

Cited By ~ 14

Author(s):

Egeria Scoditti ◽

Marika Massaro ◽

Sergio Garbarino ◽

Domenico Maurizio Toraldo

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Lung Function ◽

Pulmonary Disease ◽

Dietary Patterns ◽

Scientific Evidence ◽

Chronic Obstructive ◽

Lung Function Decline ◽

Obstructive Pulmonary Disease ◽

Prevention And Treatment ◽

The Impact

Chronic obstructive pulmonary disease is one of the leading causes of morbidity and mortality worldwide and a growing healthcare problem. Identification of modifiable risk factors for prevention and treatment of COPD is urgent, and the scientific community has begun to pay close attention to diet as an integral part of COPD management, from prevention to treatment. This review summarizes the evidence from observational and clinical studies regarding the impact of nutrients and dietary patterns on lung function and COPD development, progression, and outcomes, with highlights on potential mechanisms of action. Several dietary options can be considered in terms of COPD prevention and/or progression. Although definitive data are lacking, the available scientific evidence indicates that some foods and nutrients, especially those nutraceuticals endowed with antioxidant and anti-inflammatory properties and when consumed in combinations in the form of balanced dietary patterns, are associated with better pulmonary function, less lung function decline, and reduced risk of COPD. Knowledge of dietary influences on COPD may provide health professionals with an evidence-based lifestyle approach to better counsel patients toward improved pulmonary health.

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