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Diagnosis, Treatment and Comorbidities in Chronic Obstructive Pulmonary Disease (COPD): 2nd Edition

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Respiratory Medicine".

Deadline for manuscript submissions: closed (20 December 2025) | Viewed by 7528

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Dr. Juan Luis Rodriguez Hermosa

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1. Pulmonary Department, Research Institute of Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
2. Respiratory Department, Hospital Clinico San Carlos, 28015 Madrid, Spain
3. Department of Medicine, Universidad Complutense de Madrid, 28015 Madrid, Spain
4. Department of Medicine, Universidad Antonia de Nebrija, 28015 Madrid, Spain
Interests: COPD; bronchiectasis; alpha 1 antitrypsin deficiency; lung
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Prof. Dr. José Luis Álvarez-Sala Walther

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1. Pulmonology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain
2. Department of Medicine, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: COPD; obstructive sleep apnea; interstitial lung disease
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Dr. Myriam Calle Rubio

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1. Departamento de Medicina, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain
2. Servicio de Neumología, Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain
Interests: COPD; respiratory rehabilitation; inhaled therapy; telemedicine; biological therapies
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Special Issue Information

Dear Colleagues,

We are pleased to announce the Special Issue “Diagnosis, Treatment and Comorbidities in Chronic Obstructive Pulmonary Disease (COPD): 2nd Edition”. Building upon the success of the first edition, where we received numerous outstanding papers, we are delighted to announce this new edition.

Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitations and persistent respiratory symptoms. Various respiratory function tests, radiological tests, and clinical questionnaires are available to assess the severity and follow-up of COPD.

COPD is often associated with a number of comorbidities that have a significant impact on the overall health of patients. Cardiovascular disease, metabolic disorders, psychiatric disturbances, chronic inflammation, and the systemic effects of COPD often complicate the management of the disease.

There have been advances in the treatment of COPD, with bronchodilator drugs, LAMA and LABA, as well as inhaled corticosteroids, and different combinations of these in a single device. In the near future, biologics with new therapeutic targets will be incorporated. Non-pharmacological measures such as respiratory rehabilitation, smoking cessation, oxygen therapy and mechanical ventilation, vaccination, and lifestyle changes have been shown to improve disease prognosis.

The aim of this Special Issue is to bring together articles focusing on improving the diagnosis of COPD, the influence of comorbidities, as well as advances in the treatment of COPD, considering both the pharmacological and non-pharmacological interventions.

Dr. Juan Luis Rodriguez Hermosa
Prof. Dr. José Luis Álvarez-Sala Walther
Dr. Myriam Calle Rubio
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

COPD
diagnosis
comorbidities
respiratory rehabilitation
inhaled therapy
biological therapies

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12 pages, 649 KB

Open AccessArticle

Short-Term Effects of Dupilumab in Eosinophilic COPD

by Chiara Lupia, Daniela Pastore, Giuseppina Marrazzo, Giada Procopio, Antonio Giacalone, Federica Marrelli, Mariarosanna De Fina, Adele Emanuela De Francesco, Alessandro Vatrella, Santi Nolasco, Raffaele Campisi, Nunzio Crimi, Claudia Crimi, Girolamo Pelaia and Corrado Pelaia

J. Clin. Med. 2026, 15(2), 775; https://doi.org/10.3390/jcm15020775 - 18 Jan 2026

Viewed by 745

Abstract

Background/Objectives: Patients with eosinophilic chronic obstructive pulmonary disease (COPD) often remain symptomatic despite optimized triple inhaled therapy. Dupilumab is a fully human monoclonal antibody that blocks the IL-4 receptor alpha subunit, thereby inhibiting IL-4 and IL-13 signaling. Evidence from randomized trials supports dupilumab for add-on treatment of type 2-high COPD, but data referring to short-term effectiveness in clinical practice are quite limited. Methods: We conducted an observational, compassionate-use study enrolling 13 consecutive outpatients with eosinophilic COPD (blood eosinophils ≥ 300 cells/µL) receiving add-on biologic therapy with dupilumab 300 mg every two weeks. Clinical (CAT, mMRC), functional (spirometry and body plethysmography), and inflammatory parameters (blood eosinophils/basophils, fibrinogen, FeNO) were evaluated at baseline and after four weeks of treatment. Safety was monitored after injection in a clinical setting, as well as via weekly phone follow-up. Results: Participants (84.6% male; mean age 67.08 ± 11.42 years) experienced rapid and clinically meaningful improvements at four weeks. CAT score decreased from baseline 21.40 ± 6.22 to 14.00 ± 5.58 (p < 0.001) and mMRC scale from 2.90 ± 0.73 to 1.80 ± 0.63 (p < 0.0001), respectively. Pre-bronchodilator FEV₁ increased from baseline 1.35 ± 0.65 L to 1.59 ± 0.84 L (p < 0.05), and FVC from 2.36 ± 0.92 L to 2.83 ± 1.11 L (p < 0.01). A marked lung deflation was observed: indeed, residual volume declined from baseline 4.17 ± 1.98 L to 3.47 ± 2.07 L (p < 0.05), with a concomitant reduction in specific effective airway resistance (from baseline 3.15 ± 1.77 to 2.43 ± 1.44 kPa·s; p < 0.05) associated with significant increases in mid-expiratory flow (FEF₂₅₋₇₅: from baseline 0.62 ± 0.38 to 0.86 ± 0.71 L/s; p < 0.05) and peak expiratory flow (3.80 ± 1.40 to 4.48 ± 1.79 L/s; p < 0.01). Type 2 inflammatory biomarkers changed as follows: blood eosinophil count fell from baseline 390.0 ± 43.75 to 190.0 ± 65.47 cells/µL (p < 0.001); blood basophil number decreased from baseline 37.50 ± 13.89 to 26.25 ± 13.02 cells/µL (p < 0.001); plasma fibrinogen lowered from baseline 388.4 ± 54.81 to 334.9 ± 72.36 mg/dL (p < 0.01); FeNO levels dropped from baseline 23.95 ± 18.10 to 14.00 ± 2.04 ppb (p < 0.0001). Dupilumab was well tolerated, and no treatment-related serious adverse events or discontinuations were detected. Conclusions: Within an exploratory context of daily medical activity referring to eosinophilic COPD already treated with maximal inhaled therapy, we found relevant therapeutic effects of a four-week add-on treatment with dupilumab. In particular, our patients manifested rapid improvements in symptoms, airflow limitation, and lung hyperinflation, paralleled by significant decrements of type 2 inflammatory signatures. Such encouraging results were associated with a favorable short-term safety profile. However, larger and longer studies are necessary to corroborate these preliminary findings. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Comorbidities in Chronic Obstructive Pulmonary Disease (COPD): 2nd Edition)

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14 pages, 584 KB

Open AccessArticle

Cardiac Overload and Heart Failure Risk by NT-proBNP Levels in Older Adults with COPD Eligible for Single-Inhaler Triple Therapy: A Multicenter Longitudinal Study

by Riccardo Sarzani, Francesco Spannella, Giorgia Laureti, Piero Giordano, Federico Giulietti, Alessandro Gezzi, Pier-Valerio Mari, Angelo Coppola, Roberta Galeazzi, Yuri Rosati, Erilda Kamberi, Andrea Stronati, Alessia Resedi and Matteo Landolfo

J. Clin. Med. 2026, 15(1), 277; https://doi.org/10.3390/jcm15010277 - 30 Dec 2025

Cited by 1 | Viewed by 872

Abstract

Background: In common clinical practice, cardiac overload is still often overlooked in patients with chronic obstructive pulmonary disease (COPD) despite its substantial impact on clinical outcomes and mortality. This study aimed to assess the prevalence of cardiac overload and heart failure (HF) risk, using N-terminal pro-B-type natriuretic peptide (NT-proBNP), in older COPD patients eligible for single-inhaler triple therapy (SITT) and without history of overt HF. We also evaluated changes in NT-proBNP after 3 months of SITT. Methods: This multicenter observational study included 165 older outpatients with a recent moderate-to-severe acute exacerbation of COPD (AECOPD), categorized as ‘Group E’ according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Patients were stratified for the presence of cardiac overload and HF risk using age- and comorbidity-adjusted NT-proBNP thresholds, as recommended by the 2023 Clinical Consensus Statement of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). NT-proBNP was measured at baseline and after three months of SITT (116 patients with available test at three months). Results: Mean age was 80.7 ± 9.7 years. Patients with NT-proBNP levels indicative of “HF likely” and “HF very high-risk” were 43.0% and 24.2%, respectively. After 3 months of SITT, NT-proBNP significantly decreased by 7.2% (95%CI 9.0–5.4%, p < 0.001), with the largest reductions observed in younger patients [11.0% (95% CI 14.1–7.2%) ≤ 76 years old, 8.4% (95% CI −11.3–5.5%) in 77–87 years old, −3.0% (95% CI −6.1–0.0%) in ≥88 years old, p for interaction = 0.007]. Conclusions: In real-life clinical practice, a substantial proportion of older patients with GOLD Group E COPD had elevated NT-proBNP, suggestive of cardiac overload and high risk of HF. The early identification of these patients may prompt further cardiologic evaluation and management. After SITT and before cardiology evaluation, a significant NT-proBNP reduction has been observed, suggesting potential cardiovascular benefit of SITT. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Comorbidities in Chronic Obstructive Pulmonary Disease (COPD): 2nd Edition)

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15 pages, 1064 KB

Open AccessArticle

Muscle Unloading During Exercise: Comparative Effects of Conventional Oxygen, NIV, and High-Flow Therapy on Neural Drive in Severe COPD

by Javier Sayas-Catalán, Victoria Villena Garrido, Cristina Lalmolda, Ana Hernández-Voth, Marta Corral-Blanco, Miguel Jiménez-Gómez, Laura González-Ramos and Manel Luján

J. Clin. Med. 2025, 14(22), 8150; https://doi.org/10.3390/jcm14228150 - 17 Nov 2025

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Abstract

Objectives: This study aimed to evaluate how non-invasive ventilation (NIV) and high-flow nasal cannula therapy (HFT) versus conventional oxygen therapy (COT) affect neural ventilatory drive during exercise in patients with severe chronic obstructive pulmonary disease (COPD). Methods: We conducted an experimental, controlled study with one arm and three different conditions for the same cohort. After initial testing on conventional oxygen therapy (COT), patients exercised under NIV and HFT in sequential days and a random order. Participants: Twenty patients (mean age 60 years old (SD 3.9), 6 female) with severe COPD (30% women) on home NIV as a bridge to lung transplantation were enrolled in this study, with a mean FEV₁ of 19.78% predicted and marked hyperinflation. Protocol: Participants performed constant-load cycling exercises at 75% maximum tolerated workload under three conditions: COT, NIV, and HFT. Neuro-respiratory drive (NRD) was measured using surface parasternal and sternocleidomastoid electromyography, and mixed ANOVA was performed to analyze repeated measures across conditions. Results: In total, 20 patients were included in this study. NIV demonstrated superior performance, with 60% lower NRD compared to COT (488.81 µV vs. 1180.63 µV, p < 0.05). HFT showed intermediate effects (807.8 µV). NIV also achieved greater reduction in respiratory rate (4.2 breaths/min), lower perceived exertion (Borg score decrease: 1.8 points), and more pronounced CO₂ reduction (5.3 mmHg) compared to both COT and HFT. Conclusions: NIV significantly reduces NRD during exercise in severe COPD patients compared to HFT and COT. This supports its use as a valuable adjunct to pulmonary rehabilitation in severe COPD. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Comorbidities in Chronic Obstructive Pulmonary Disease (COPD): 2nd Edition)

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28 pages, 2677 KB

Open AccessArticle

Sex-Based Disparities in Clinical Burden and Diagnostic Delay in COPD: Insights from Primary Care

by Myriam Calle Rubio, Soha Esmaili, Iman Esmaili, Lucia Gómez Martín-Caro, Sofia Ayat Ortiz and Juan Luis Rodríguez Hermosa

J. Clin. Med. 2025, 14(17), 6258; https://doi.org/10.3390/jcm14176258 - 4 Sep 2025

Cited by 2 | Viewed by 1098

Abstract

Background. Sex-based disparities in chronic obstructive pulmonary disease (COPD) diagnosis remain underexplored, particularly in primary care settings. This study assessed sex differences in clinical burden, diagnostic delay, and missed diagnostic opportunities using conventional and composite metrics. Methods. A cross-sectional analysis was conducted in 166 newly diagnosed COPD patients (76 women, 90 men) from Spanish primary care. Clinical severity, healthcare use, and diagnostic timing were compared using Mann–Whitney and chi-squared tests. Composite indices included the Symptom Intensity Score, Diagnostic Inertia Indices, DOSE Index, and Diagnosis Complexity Score. Multivariable regressions evaluated independent associations. Results. At diagnosis, women showed a greater clinical and functional burden (FEV₁ % predicted: 50.4% vs. 61.4%, p < 0.001; symptom intensity z-score: 0.13 vs. −0.67, p < 0.001), higher diagnostic complexity (Diagnosis Complexity Score: 403.5 vs. 272.0, p < 0.001), and longer diagnostic delay (median: 133.0 vs. 66.5 days, p < 0.001). Stratified and composite analyses confirmed consistent sex-based asymmetries. In adjusted models, being female independently predicted a longer diagnostic delay (β = 0.888, p = 0.005), but was not significantly associated with the burden of missed diagnostic opportunities (MDOs) (β = 0.112, p = 0.395). Conclusions. Women with newly diagnosed COPD experience greater symptom burden and longer diagnostic delays. Composite metrics may improve the identification of diagnostic disparities in routine clinical settings. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Comorbidities in Chronic Obstructive Pulmonary Disease (COPD): 2nd Edition)

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12 pages, 705 KB

Open AccessArticle

Impact of Acute Kidney Injury on Mortality Outcomes in Patients Hospitalized for COPD Exacerbation: A National Inpatient Sample Analysis

by Zeina Morcos, Rachel Daniel, Mazen Hassan, Hamza Qandil, Chloe Lahoud, Chapman Wei and Suzanne El Sayegh

J. Clin. Med. 2025, 14(15), 5393; https://doi.org/10.3390/jcm14155393 - 31 Jul 2025

Viewed by 1726

Abstract

Background/Objectives: Acute kidney injury (AKI) worsens outcomes in COPD exacerbation (COPDe), yet limited data compare the demographics and mortality risk factors of COPDe admissions with and without AKI. Understanding this association may enhance risk stratification and management strategies. The aim of this study was to identify demographic differences and mortality risk factors in COPDe admissions with and without AKI. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) from 1 January 2016 to 1 January 2021. Patients aged ≥ 35 years with a history of smoking and a diagnosis of COPDe were included. Patients with CKD stage 5, end-stage kidney disease (ESKD), heart failure decompensation, urinary tract infections, myocardial infarction, alpha-1 antitrypsin deficiency, or active COVID-19 infection were excluded. Baseline demographics were analyzed using descriptive statistics. Multivariate logistic regression analysis was used to measure the odds ratio (OR) of mortality. Statistical analyses were conducted using IBM SPSS Statistics V.30, with statistical significance at p < 0.05. Results: Among 405,845 hospitalized COPDe patients, 13.6% had AKI. These patients were older, had longer hospital stays, and included fewer females and White patients. AKI was associated with significantly higher mortality (OR: 2.417), more frequent acute respiratory failure (OR: 4.559), intubation (OR: 10.262), and vasopressor use (OR: 2.736). CVA, pneumonia, and pulmonary hypertension were significant mortality predictors. Hypertension, CAD, and diabetes were associated with lower mortality. Conclusions: AKI in COPDe admissions is associated with worse outcomes. Protective effects from certain comorbidities may relate to renoprotective medications. Study limitations include coding errors and retrospective design. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Comorbidities in Chronic Obstructive Pulmonary Disease (COPD): 2nd Edition)

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24 pages, 3765 KB

Open AccessSystematic Review

Effect of Chronic Obstructive Pulmonary Disease (COPD) on Biventricular Mechanics in Patients Without Severe Airflow Obstruction

by Andrea Sonaglioni, Massimo Baravelli, Antonella Caminati, Federico Tagariello, Federico De Cesco, Gian Luigi Nicolosi, Michele Lombardo and Sergio Harari

J. Clin. Med. 2025, 14(11), 3660; https://doi.org/10.3390/jcm14113660 - 23 May 2025

Cited by 1 | Viewed by 1592

Abstract

Background: Over the last 15 years, few echocardiographic studies have examined the biventricular mechanics by speckle tracking echocardiography (STE) in patients affected by chronic obstructive pulmonary disease (COPD) without advanced lung disease. We aimed to summarize the main findings of these studies and quantify the overall effect of COPD on biventricular mechanics in patients without severe airflow obstruction. Methods: Eligible studies assessing cardiac function by conventional transthoracic echocardiography (TTE), implemented with a STE analysis of left ventricular (LV)-global longitudinal strain (GLS) and/or right ventricular (RV)-GLS in COPD patients without severe airflow obstruction vs. healthy controls, were selected from the PubMed, Embase and Scopus databases. The primary endpoint was to quantify the effect of COPD on LV-GLS and RV-GLS in individuals without advanced lung disease. Continuous data [LV-GLS, RV-GLS, left ventricular ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE)] were pooled as the standardized mean difference (SMD) comparing COPD cohorts with healthy controls. Results: Ten studies were included, totaling 682 COPD patients and 316 healthy controls. Overall, COPD showed a large effect on LV-GLS (SMD −1.296; 95%CI −2.010, −0.582, p < 0.001) and RV-GLS (SMD −1.474; 95% CI −2.142, −0.805, p < 0.001), a medium-to-large effect on TAPSE (SMD −0.783, 95% CI −0.949, −0.618, p < 0.001) and a small effect on LVEF (SMD −0.366, 95% CI −0.659, −0.074, p = 0.014). The I² statistic value for the LV-GLS (91.1%), RV-GLS (88.2%) and LVEF (76.7%) studies suggested a high between-study heterogeneity, while that for the TAPSE (38.1%) studies was compatible with a low-to-moderate between-study heterogeneity. Egger’s test yielded a p-value of 0.16, 0.48, 0.58 and 0.50 for LV-GLS, RV-GLS, LVEF and TAPSE studies, respectively, indicating an absence of publication bias. Meta-regression analyses excluded that the effect of COPD on biventricular mechanics might be influenced by potential confounders (all p > 0.05). Sensitivity analysis confirmed the robustness of the LV-GLS, RV-GLS and TAPSE studies’ results. Conclusions: COPD appears to be independently associated with a mild attenuation of biventricular mechanics in patients with moderate airflow limitations, despite a preserved LVEF and TAPSE on conventional TTE. STE analysis may allow clinicians to identify COPD patients with subclinical myocardial dysfunction and an increased risk of heart failure and cardiovascular complications early. Full article

(This article belongs to the Special Issue Diagnosis, Treatment and Comorbidities in Chronic Obstructive Pulmonary Disease (COPD): 2nd Edition)

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