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10 pages, 1385 KiB

Open AccessArticle

Gender Difference in the Relationship between Extrapulmonary Factors and Reduced Lung Function in Early Adulthood

by Keiko Doi, Tsunahiko Hirano, Keiji Oishi, Ayumi Fukatsu-Chikumoto, Yuichi Ohteru, Kazuki Hamada, Shuichiro Ohata, Yoriyuki Murata, Yoshikazu Yamaji, Maki Asami-Noyama, Nobutaka Edakuni, Tomoyuki Kakugawa and Kazuto Matsunaga

J. Clin. Med. 2024, 13(6), 1769; https://doi.org/10.3390/jcm13061769 - 19 Mar 2024

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Abstract

(1) Background: Reduced lung function in early adulthood is associated with future risks to health outcomes that have not been fully explored by gender. We investigated gender-specific relationships between lung function and extrapulmonary variables, assessing their potential as screening markers for respiratory [...] Read more.

(1) Background: Reduced lung function in early adulthood is associated with future risks to health outcomes that have not been fully explored by gender. We investigated gender-specific relationships between lung function and extrapulmonary variables, assessing their potential as screening markers for respiratory dysfunction in young adults. (2) Methods: The participants were 151 medical students. Clinical data, handgrip strength (HS); body composition parameters such as skeletal muscle mass index (SMI), whole-body phase angle (WBPhA), and bone mineral content (BMC); and pulmonary function variables, vital capacity (VC), forced VC (FVC), and forced expiratory volume in one second (FEV₁), were measured. (3) Results: FEV₁ was significantly correlated with BMI, SMI, WBPhA, BMC, and both left and right HS (p < 0.0001, respectively) across all participants. According to gender, FEV₁ had the strongest positive association with left HS in males (p < 0.0001) and BMC in females (p < 0.0001). The area under the curve for detecting the bottom quartile of FEV₁ was 0.705 (cut-off 41.0 kg, sensitivity 91%) for left HS in males and 0.742 (cut-off 2.11 kg, sensitivity 81%) for BMC in females. (4) Conclusions: Gender-specific relationships between intrapulmonary and extrapulmonary factors such as left HS and BMC could be useful for screening suspected respiratory dysfunction in early adulthood. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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11 pages, 1062 KiB

Open AccessArticle

Impulse Oscillometry as a Diagnostic Test for Pulmonary Emphysema in a Clinical Setting

by Allan Klitgaard, Anders Løkke and Ole Hilberg

J. Clin. Med. 2023, 12(4), 1547; https://doi.org/10.3390/jcm12041547 - 15 Feb 2023

Cited by 1 | Viewed by 1401

Abstract

Body plethysmography (BP) is the standard pulmonary function test (PFT) in pulmonary emphysema diagnosis, but not all patients can cooperate to this procedure. An alternative PFT, impulse oscillometry (IOS), has not been investigated in emphysema diagnosis. We investigated the diagnostic accuracy of IOS [...] Read more.

Body plethysmography (BP) is the standard pulmonary function test (PFT) in pulmonary emphysema diagnosis, but not all patients can cooperate to this procedure. An alternative PFT, impulse oscillometry (IOS), has not been investigated in emphysema diagnosis. We investigated the diagnostic accuracy of IOS in the diagnosis of emphysema. Eighty-eight patients from the pulmonary outpatient clinic at Lillebaelt Hospital, Vejle, Denmark, were included in this cross-sectional study. A BP and an IOS were performed in all patients. Computed tomography scan verified presence of emphysema in 20 patients. The diagnostic accuracy of BP and IOS for emphysema was evaluated with two multivariable logistic regression models: Model 1 (BP variables) and Model 2 (IOS variables). Model 1 had a cross-validated area under the ROC curve (CV-AUC) = 0.892 (95% CI: 0.654–0.943), a positive predictive value (PPV) = 59.3%, and a negative predictive value (NPV) = 95.0%. Model 2 had a CV-AUC = 0.839 (95% CI: 0.688–0.931), a PPV = 55.2%, and an NPV = 93.7%. We found no statistically significant difference between the AUC of the two models. IOS is quick and easy to perform, and it can be used as a reliable rule-out method for emphysema. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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11 pages, 21119 KiB

Open AccessArticle

The Impact of Air Pollution on Frequent Exacerbations among COPD Patients: An Observational Study on the Population of Western Romania

by Gabriel-Petrică Bălă, Bogdan Timar, Florin Gorun, Radu Motisan, Camelia Pescaru, Emanuela Tudorache, Monica Marc, Diana Manolescu, Cosmin Citu and Cristian Oancea

J. Clin. Med. 2022, 11(15), 4352; https://doi.org/10.3390/jcm11154352 - 27 Jul 2022

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Abstract

Patients with respiratory pathologies are the risk group most affected by air pollution, being directly exposed, especially those diagnosed with chronic obstructive pulmonary disease (COPD). In this observational study, which included 79 patients, we evaluated whether COPD patients with the frequent exacerbating phenotype [...] Read more.

Patients with respiratory pathologies are the risk group most affected by air pollution, being directly exposed, especially those diagnosed with chronic obstructive pulmonary disease (COPD). In this observational study, which included 79 patients, we evaluated whether COPD patients with the frequent exacerbating phenotype or the infrequent exacerbating phenotype live in residences with higher values of air pollution. An air quality monitoring station was installed in each patient’s house for at least 24 h and PM 1.0, PM 2.5, and PM 10 were measured. Average PM 1.0, PM 2.5, and PM 10 values were lower in the group of infrequently exacerbating patients compared to the frequently exacerbating ones. For every 1 µg/m³ increase in the average values of PM 1.0, PM 2.5, and PM 10, there is an increase of 1.7%, 1.8% and 1%, respectively, in the risk of developing exacerbations. More importantly, an average value of PM 1.0, PM 2.5, and PM 10 above 32.21 µg/m³, 82.32 µg/m³ and 42.89 µg/m³ increases the probability of developing an exacerbation by 3.83, 10.14, and 4.12 times, respectively. Our analysis showed that COPD patients with a frequently exacerbating phenotype live in residences with high levels of air pollution compared to infrequently exacerbating ones. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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14 pages, 1499 KiB

Open AccessArticle

Use of Inhaled Corticosteroids and Risk of Acquiring Haemophilus influenzae in Patients with Chronic Obstructive Pulmonary Disease

by Raza Ul Mohsin, Christian Kjer Heerfordt, Josefin Eklöf, Pradeesh Sivapalan, Mohamad Isam Saeed, Truls Sylvan Ingebrigtsen, Susanne Dam Nielsen, Zitta Barrella Harboe, Kasper Karmark Iversen, Jette Bangsborg, Jens Otto Jarløv, Jonas Bredtoft Boel, Christian Østergaard Andersen, Henrik Pierre Calum, Ram B. Dessau and Jens-Ulrik Stæhr Jensen

J. Clin. Med. 2022, 11(12), 3539; https://doi.org/10.3390/jcm11123539 - 20 Jun 2022

Cited by 5 | Viewed by 1756

Abstract

Background: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD), despite the known risk of severe adverse effects including pulmonary infections. Research Question: Our study investigates the risk of acquiring a positive Haemophilus influenzae airway culture with use of ICS [...] Read more.

Background: Inhaled corticosteroids (ICS) are widely used in chronic obstructive pulmonary disease (COPD), despite the known risk of severe adverse effects including pulmonary infections. Research Question: Our study investigates the risk of acquiring a positive Haemophilus influenzae airway culture with use of ICS in outpatients with COPD. Study Design and Methods: We conducted an epidemiological cohort study using data from 1 January 2010 to 19 February 2018, including 21,218 outpatients with COPD in Denmark. ICS use 365 days prior to cohort entry was categorised into low, moderate, and high, based on cumulated ICS dose extracted from a national registry on reimbursed prescriptions. A Cox proportional hazards regression model was used to assess the future risk of acquiring H. Influenzae within 365 days from cohort entry, and sensitivity analyses were performed using propensity score matched models. Results: In total, 801 (3.8%) patients acquired H. Influenzae during follow-up. Use of ICS was associated with a dose-dependent increased risk of acquiring H. Influenzae with hazard ratio (HR) 1.2 (95% confidence interval (CI) 0.9–1.5, p value = 0.1) for low-dose ICS; HR 1.7 (95% CI 1.3–2.1, p value < 0.0001) for moderate dose; and HR 1.9 (95% CI 1.5–2.4, p value < 0.0001) for high-dose ICS compared to no ICS use. Results were confirmed in the propensity-matched model using the same categories. Conclusions: ICS use in outpatients with COPD was associated with a dose-dependent increase in risk of isolating H. Influenzae. This observation supports that high dose ICS should be used with caution. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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13 pages, 11961 KiB

Open AccessArticle

A New Dyspnea Evaluation System Focusing on Patients’ Perceptions of Dyspnea and Their Living Disabilities: The Linkage between COPD and Frailty

by Keiji Oishi, Kazuto Matsunaga, Misa Harada, Junki Suizu, Keita Murakawa, Ayumi Chikumoto, Yuichi Ohteru, Kazuki Matsuda, Sho Uehara, Kazuki Hamada, Shuichiro Ohata, Yoriyuki Murata, Yoshikazu Yamaji, Maki Asami-Noyama, Nobutaka Edakuni, Tomoyuki Kakugawa and Tsunahiko Hirano

J. Clin. Med. 2020, 9(11), 3580; https://doi.org/10.3390/jcm9113580 - 06 Nov 2020

Cited by 9 | Viewed by 2600

Abstract

Background: As much as there are unmet needs for brief frailty assessment in patients with chronic obstructive pulmonary disease (COPD), the lack of a simplified and comprehensive dyspnea evaluation system that focuses on the patients’ perceptions of dyspnea and their COPD living disabilities [...] Read more.

Background: As much as there are unmet needs for brief frailty assessment in patients with chronic obstructive pulmonary disease (COPD), the lack of a simplified and comprehensive dyspnea evaluation system that focuses on the patients’ perceptions of dyspnea and their COPD living disabilities remains a major challenge. We developed patient-reported outcome measures for dyspnea-related behavior and activity limitation (PROMs-D), which consisted of the Activity-limit Dyspnea Scale (ADS) and Self-Limit Dyspnea Scale (SDS), while investigated the usefulness of PROMs-D in identifying frailty. Methods: We administered PROMs-D and frailty status evaluations in 128 outpatients. Results: We classified 30 (23.4%), 50 (39.0%), and 48 (37.5%) patients as robust, prefrail, and frail, respectively. There was a positive correlation between SDS and ADS (ρ = 0.67, p < 0.001), and both ADS and SDS had high accuracies for detecting frailty (AUC, 0.82 and 0.78, respectively). Moreover, a PROMs-D score that consisted of the sum of ADS and SDS was more effective in stratifying frailty (cutoff value, 2; AUC, 0.85; sensitivity, 60%; specificity, 95%). Conclusions: PROMs-D could be used as the first step for frailty screening in patients with COPD, and we propose the importance of capturing the troublesome nature of living behaviors due to dyspnea in daily clinical practice. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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12 pages, 995 KiB

Open AccessArticle

Correlation of Arterial CO₂ and Respiratory Impedance Values among Subjects with COPD

by Tomoki Uno, Tetsuya Homma, Masahiko Shigemura, Yosuke Fukuda, Tomoyuki Kimura, Chihiro Onitsuka, Tomoko Kawahara, Hiroki Sato, Kaho Akimoto, Hiromitsu Suganuma, Ayaka Kashima, Shigenori Yamamoto, Takaya Ebato, Tomohiro Matsunaga, Keisuke Kaneko, Hatsuko Mikuni, Haruna Sato, Yoshitaka Uchida, Akiko Fujiwara, Naota Kuwahara, Ryo Manabe, Hitomi Ida, Kuniaki Hirai, Yoshito Miyata, Megumi Jinno, Shin Ohta, Yasunari Kishino, Hideki Inoue, Mayumi Yamamoto, Yoshio Watanabe, Sojiro Kusumoto, Koichi Ando, Shintaro Suzuki, Akihiko Tanaka, Tohru Ohmori and Hironori Sagara Show full author list Hide full author list

J. Clin. Med. 2020, 9(9), 2819; https://doi.org/10.3390/jcm9092819 - 31 Aug 2020

Cited by 1 | Viewed by 2698

Abstract

Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk [...] Read more.

Chronic obstructive pulmonary disease (COPD) is a respiratory illness characterized by airflow limitation and chronic respiratory symptoms with a global prevalence estimated to be more than 10% in 2010 and still on the rise. Furthermore, hypercapnic subject COPD leads to an increased risk of mortality, morbidity, and poor QoL (quality of life) than normocapnic subjects. Series of studies showed the usefulness of the forced oscillation technique (FOT) to measure small airway closure. Traditional findings suggested that hypercapnia may not be the main treating targets, but recent findings suggested that blood stream CO₂ may lead to a worse outcome. This study aimed to seek the relationship between CO₂ and small airway closure by using FOT. Subjects with COPD (n = 124; hypercapnia 22 and normocapnia 102) were analyzed for all pulmonary function values, FOT values, and arterial blood gas analysis. Student’s t-test, Spearman rank correlation, and multi linear regression analysis were used to analyze the data. COPD subjects with hypercapnia showed a significant increase in R5, R20, Fres, and ALX values, and a greater decrease in X5 value than normocapnic patients. Also, multiple linear regression analysis showed R5 was associated with hypercapnia. Hypercapnia may account for airway closure among subjects with COPD and this result suggests treating hypercapnia may lead to better outcomes for such a subject group. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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11 pages, 1556 KiB

Open AccessArticle

A Novel Role of Growth Differentiation Factor (GDF)-15 in Overlap with Sedentary Lifestyle and Cognitive Risk in COPD

by Tsunahiko Hirano, Keiko Doi, Kazuto Matsunaga, Shun Takahashi, Tomohiro Donishi, Kazuyoshi Suga, Keiji Oishi, Kasumi Yasuda, Yusuke Mimura, Misa Harada, Sumiteru Suizu, Keita Murakawa, Ayumi Chikumoto, Yuichi Ohteru, Kazuki Matsuda, Sho Uehara, Kazuki Hamada, Shuichiro Ohata, Yoriyuki Murata, Yoshikazu Yamaji, Maki Asami-Noyama, Nobutaka Edakuni and Tomoyuki Kakugawa Show full author list Hide full author list

J. Clin. Med. 2020, 9(9), 2737; https://doi.org/10.3390/jcm9092737 - 24 Aug 2020

Cited by 16 | Viewed by 2929

Abstract

Sedentary behavior and cognitive impairment have a direct impact on patients’ outcomes. An energy metabolic disorder may be involved in the overlap of these comorbid conditions (motoric cognitive risk (MCR)) in patients with chronic obstructive pulmonary disease (COPD). We aimed to explore the [...] Read more.

Sedentary behavior and cognitive impairment have a direct impact on patients’ outcomes. An energy metabolic disorder may be involved in the overlap of these comorbid conditions (motoric cognitive risk (MCR)) in patients with chronic obstructive pulmonary disease (COPD). We aimed to explore the linkage between a proapoptotic protein, growth differentiation factor (GDF)-15, and MCR. Physical activity (PA), cognitive function (Japanese version of the Montreal Cognitive Assessment: MOCA-J), and the serum GDF-15 levels were assessed in healthy subjects (n = 14), asthmatics (n = 22), and COPD patients (n = 28). In the entire cohort, serum GDF-15 had negative correlations with exercise (Ex) (ρ = −0.43, p < 0.001) and MoCA-J (ρ = −0.44, p < 0.001), and Ex and MOCA-J showed a positive correlation (ρ = 0.52, p < 0.0001). Compared to healthy subjects and asthmatics, COPD patients showed the highest serum GDF-15 levels and had a significantly higher proportion of subjects with MCR (both sedentary lifestyle (EX < 1.5) and cognitive risk (MoCA-J ≤ 25)). Also, we found that serum GDF-15 has a screening potential (100% sensitivity) greater than aging (67% sensitivity) for detecting MCR in COPD patients. In conclusion, higher serum GDF-15 had interrelationships with a sedentary lifestyle and cognitive risk. This protein was not disease-specific but could be a screening biomarker to detect MCR related to poor health outcomes of COPD patients. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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12 pages, 1436 KiB

Open AccessArticle

Heart Failure is Highly Prevalent and Difficult to Diagnose in Severe Exacerbations of COPD Presenting to the Emergency Department

by Mariaenrica Tinè, Erica Bazzan, Umberto Semenzato, Davide Biondini, Elisabetta Cocconcelli, Elisabetta Balestro, Alvise Casara, Simonetta Baraldo, Graziella Turato, Manuel G. Cosio and Marina Saetta

J. Clin. Med. 2020, 9(8), 2644; https://doi.org/10.3390/jcm9082644 - 14 Aug 2020

Cited by 11 | Viewed by 2816

Abstract

Background: Some 20% of patients with stable Chronic Obstructive Pulmonary Disease (COPD) might have heart failure (HF). HF contribution to acute exacerbations of COPD (AECOPD) presenting to the emergency department (ED) is not well established. Aims: To assess (1) the HF incidence in [...] Read more.

Background: Some 20% of patients with stable Chronic Obstructive Pulmonary Disease (COPD) might have heart failure (HF). HF contribution to acute exacerbations of COPD (AECOPD) presenting to the emergency department (ED) is not well established. Aims: To assess (1) the HF incidence in patients presenting to the ED with AECOPD; (2) the concordance between ED and respiratory ward (RW) diagnosis; (3) the factors associated with risk of death after hospital discharge. Methods: Retrospective chart review of 119 COPD patients presenting to ED for acute exacerbation of respiratory symptoms and then admitted to RW where a final diagnosis of AECOPD, AECOPD and HF and AECOPD and OD (other diagnosis), was obtained. ED and RW diagnosis were then compared. Factors affecting survival at follow-up were investigated. Results: At RW, 40.3% of cases were diagnosed of AECOPD, 40.3% of AECOPD and HF and 19.4% of AECOPD and OD, with ED diagnosis coinciding with RW’s in 67%, 23%, and 57% of cases respectively. At RW, 60% of patients in GOLD1 had HF, of which 43% were diagnosed at ED, while 40% in GOLD4 had HF that was never diagnosed at ED. Lack of inclusion in a COPD care program, HF, and early readmission for AECOPD were associated with mortality. Conclusions: HF is highly prevalent and difficult to diagnose in patients in all GOLD stages presenting to the ED with severe AECOPD, and along with lack of inclusion in a COPD care program, confers a high risk for mortality. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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13 pages, 1383 KiB

Open AccessArticle

Stable Clinical Course of Chronic Obstructive Pulmonary Disease Patients in the Era of Double Bronchodilator Therapy: A Single Referral Center Experience

by Sun Hye Shin, Noeul Kang, Juhee Cho, Yeonseok Choi, Hyun Kyu Cho, Hye Sook Choi, Hojoong Kim, Jun Hyeok Lim and Hye Yun Park

J. Clin. Med. 2020, 9(8), 2547; https://doi.org/10.3390/jcm9082547 - 06 Aug 2020

Viewed by 2312

Abstract

Despite clinical benefits of long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) double bronchodilator therapy, there has been limited evidence for treatment change from LAMA/LABA to inhaled corticosteroid (ICS)-containing therapy. This study aimed to assess the rate of ICS-containing therapy from LAMA/LABA and investigate the [...] Read more.

Despite clinical benefits of long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) double bronchodilator therapy, there has been limited evidence for treatment change from LAMA/LABA to inhaled corticosteroid (ICS)-containing therapy. This study aimed to assess the rate of ICS-containing therapy from LAMA/LABA and investigate the factors associated with ICS addition. Between October 2015 and March 2019, consecutive patients prescribed with a LAMA/LABA fixed-dose combinations (FDCs) therapy without ICS were retrospectively identified from a single-referral hospital. The primary outcome was addition of ICS. During LAMA/LABA FDCs therapy (median, 12.4 months), 47 (17.7%) out of 266 patients had ICS addition. Most patients maintained bronchodilators without addition of ICS at 12 (86.5%) or 24 (76.8%) months. Patients with dyspnea (mMRC ≥ 2) at baseline, previous ICS use, and exacerbation in the previous year were at a higher risk of ICS addition. Especially, exacerbation in the previous year and dyspnea were associated with the development of frequent exacerbations during LAMA/LABA FDCs therapy, which might have led to ICS addition. Double bronchodilator therapy could be well-maintained in stable COPD patients. However, patients with exacerbation in the previous year, dyspnea, and previous ICS use should be closely approached and monitored with initiation of LAMA/LABA FDCs therapy without ICS. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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13 pages, 2576 KiB

Open AccessArticle

Decline in Carbon Monoxide Transfer Coefficient in Chronic Obstructive Pulmonary Disease

by Yeon Wook Kim, Chang-Hoon Lee, Hun-Gyu Hwang, Yu-Il Kim, Deog-Kyeom Kim, Yeon-Mok Oh, Sang Haak Lee, Ki Uk Kim and Sang-Do Lee

J. Clin. Med. 2020, 9(5), 1512; https://doi.org/10.3390/jcm9051512 - 18 May 2020

Cited by 3 | Viewed by 2419

Abstract

Background: Although a reduced carbon monoxide transfer coefficient (Kco) is an important feature in chronic obstructive pulmonary disease (COPD), how it changes over time and its relationship with other clinical outcomes remain unclear. This study evaluated longitudinal changes in Kco and their relationship [...] Read more.

Background: Although a reduced carbon monoxide transfer coefficient (Kco) is an important feature in chronic obstructive pulmonary disease (COPD), how it changes over time and its relationship with other clinical outcomes remain unclear. This study evaluated longitudinal changes in Kco and their relationship with other clinical outcomes. Methods: We evaluated patients with COPD from the Korean Obstructive Lung Disease cohort, followed up for up to ten years. Random coefficient models were used to assess the annual change in Kco over time. Participants were categorized into tertiles according to Kco decline rate. Baseline characteristics and outcomes, including changes in FEV1 and emphysema index, incidence of exacerbations, and mortality, were compared between categories. Results: A decline in Kco was observed in 92.9% of the 211 enrolled participants with COPD. Those with the most rapid decline (tertile 1) had a lower FEV1/FVC% (tertile 1: 43.8% ± 9.7%, tertile 2: 46.4% ± 10.5%, tertile 3: 49.2% ± 10.4%, p = 0.008) and a higher emphysema index at baseline (27.7 ± 14.8, 22.4 ± 16.1, 18.1 ± 14.5, respectively, p = 0.001). Tertile 3 showed a lower decline rate in FEV1 (16.3 vs. 27.1 mL/yr, p = 0.017) and a lower incidence of exacerbations (incidence rate ratio = 0.66, 95% CI = 0.44–0.99) than tertile 1. There were no differences in the change in emphysema index and mortality between categories. Conclusion: Most patients with COPD experienced Kco decline over time, which was greater in patients with more severe airflow limitation and emphysema. Decline in Kco was associated with an accelerated decline in FEV1 and more frequent exacerbations; hence, this should be considered as an important outcome measure in further studies. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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15 pages, 2837 KiB

Open AccessArticle

Roflumilast in Severely Ill Patients with Chronic Obstructive Pulmonary Disease with Frequent Exacerbations: Risk of Pneumonia Hospitalization and Severe Exacerbations

by Imane Achir Alispahic, Rikke Sørensen, Josefin Eklöf, Pradeesh Sivapalan, Anders Løkke, Niels Seersholm, Jakob Hedemark Vestergaard and Jens-Ulrik Stæhr Jensen

J. Clin. Med. 2020, 9(5), 1442; https://doi.org/10.3390/jcm9051442 - 12 May 2020

Cited by 2 | Viewed by 3013

Abstract

Roflumilast is given as an add-on to inhalation medication in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Animal experiments have documented deleterious effects of roflumilast in bacterial infections, but trials have not reported the risk of bacterial infections in patients. [...] Read more.

Roflumilast is given as an add-on to inhalation medication in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis. Animal experiments have documented deleterious effects of roflumilast in bacterial infections, but trials have not reported the risk of bacterial infections in patients. The objective of this study is to determine, among outpatients with severe COPD in a two-year follow-up period, the risk of hospitalization-requiring pneumonia, severe acute exacerbation in COPD (AECOPD-hosp), and death. Patients with COPD using roflumilast (roflumilast users) were compared to a propensity score-matched COPD control group not using roflumilast (non-roflumilast users). Roflumilast users had an increased 2-year risk of hospitalization-requiring pneumonia (HR 1.5, 95% CI 1.3 to 1.8, p-value < 0.0001) compared to controls, and of AECOPD-Hosp (hazard ratio(HR) 1.6, 95%, confidence interval (CI) 1.5 to 1.8, p-value < 0.0001) and. When adding an active comparator (theophylline) as a matching variable, the signal was largely unchanged. In conclusion, roflumilast was associated with an increased number of hospitalizations for pneumonia and for AECOPD. Since trials have not reported risks of bacterial complications and data regarding severe exacerbations in roflumilast users are sparse and diverging, these data are concerning. Trials focused on the risk of pneumonia, AECOPD, and other bacterial infections in roflumilast users are needed urgently. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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16 pages, 818 KiB

Open AccessArticle

NIV Is not Adequate for High Intensity Endurance Exercise in COPD

by Tristan Bonnevie, Francis-Edouard Gravier, Emeline Fresnel, Adrien Kerfourn, Clément Medrinal, Guillaume Prieur, Yann Combret, Jean-François Muir, Antoine Cuvelier, David Debeaumont, Gregory Reychler, Maxime Patout and Catherine Viacroze

J. Clin. Med. 2020, 9(4), 1054; https://doi.org/10.3390/jcm9041054 - 08 Apr 2020

Cited by 4 | Viewed by 2840

Abstract

Noninvasive ventilation (NIV) during exercise has been suggested to sustain higher training intensity but the type of NIV interface, patient-ventilator asynchronies (PVA) or technological limitation of the ventilator may interfere with exercise. We assessed whether these parameters affect endurance exercise capacity in severe [...] Read more.

Noninvasive ventilation (NIV) during exercise has been suggested to sustain higher training intensity but the type of NIV interface, patient-ventilator asynchronies (PVA) or technological limitation of the ventilator may interfere with exercise. We assessed whether these parameters affect endurance exercise capacity in severe COPD patients. In total, 21 patients with severe COPD not eligible to home NIV performed three constant workload tests. The first test was carried out on spontaneous breathing (SB) and the following ones with NIV and a nasal or oronasal mask in a randomized order. PVA and indicators of ventilator performance were assessed through a comprehensive analysis of the flow pressure tracing raw data from the ventilator. The time limit was significantly reduced with both masks (406 s (197–666), 240 s (131–385) and 189 s (115–545), p < 0.01 for tests in SB, with oronasal and nasal mask, respectively). There were few PVA with an oronasal mask (median: 3.4% (1.7–5.2)) but the ventilator reached its maximal generating capacity (median flowmax: 208.0 L/s (189.5–224.8) while inspiratory pressure dropped throughout exercise (from 10.1 (9.4–11.4) to 8.8 cmH2O (8.6–10.8), p < 0.01). PVA were more frequent with nasal mask (median: 12.8% (3.2–31.6), p < 0.01). Particularly, the proportion of patients with ineffective efforts > 10% was significantly higher with nasal interface (0% versus 33.3%, p < 0.01). NIV did not effectively improve endurance capacity in COPD patients not acclimated to home NIV. This was due to a technological limitation of the ventilator for the oronasal mask and the consequence either of an insufficient pressure support or a technological limitation for the nasal mask. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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9 pages, 426 KiB

Open AccessArticle

Differences in the Outcome of Patients with COPD according to Body Mass Index

by Zichen Ji, Javier de Miguel-Díez, Christian Reynaldo Castro-Riera, José María Bellón-Cano, Virginia Gallo-González, Walther Iván Girón-Matute, Rodrigo Jiménez-García, Ana López-de Andrés, Virginia Moya-Álvarez, Luis Puente-Maestu and Julio Hernández-Vázquez

J. Clin. Med. 2020, 9(3), 710; https://doi.org/10.3390/jcm9030710 - 05 Mar 2020

Cited by 17 | Viewed by 2833

Abstract

Background: In chronic obstructive pulmonary disease (COPD), the “obesity paradox” is a phenomenon without a clear cause. The objective is to analyze the complications of COPD patients according to their body mass index (BMI). Methods: An observational study with a six-year prospective follow-up [...] Read more.

Background: In chronic obstructive pulmonary disease (COPD), the “obesity paradox” is a phenomenon without a clear cause. The objective is to analyze the complications of COPD patients according to their body mass index (BMI). Methods: An observational study with a six-year prospective follow-up of 273 COPD patients who attended a spirometry test in 2011. Survival and acute events were analyzed according to the BMI quartiles. Results: A total of 273 patients were included. BMI quartiles were ≤24.23; 24.24–27.69; 27.70–31.25; ≥31.26. During the follow-up, 93 patients died. No differences were found in exacerbations, pneumonia, emergency visits, hospital admissions or income in a critical unit. Survival was lower in the quartile 1 of BMI with respect to each of the 2–4 quartiles (p-value 0.019, 0.013, and 0.004, respectively). Advanced age (hazard ratio, HR 1.06; 95% confidence interval, CI 1.03–1.09), low pulmonary function (HR 0.93; 95% CI 0.86–0.99), exacerbator with chronic bronchitis phenotype (HR 1.76; 95% CI 1.01–3.06), high Charlson (HR 1.32, 95% CI 1.18–1.49), and the quartile 1 of BMI (HR 1.99, 95% CI 1.08–3.69) were identified as risk factors independently associated with mortality. Conclusions: In COPD, low BMI conditions a lower survival, although not for having more acute events. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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14 pages, 440 KiB

Open AccessArticle

Risk Factors for Postural and Functional Balance Impairment in Patients with Chronic Obstructive Pulmonary Disease

by Jaekwan K. Park, Nicolaas E. P. Deutz, Clayton L. Cruthirds, Sarah K. Kirschner, Hangue Park, Michael L. Madigan and Mariëlle P. K. J. Engelen

J. Clin. Med. 2020, 9(2), 609; https://doi.org/10.3390/jcm9020609 - 24 Feb 2020

Cited by 11 | Viewed by 3499

Abstract

Reduced balance function has been observed during balance challenging conditions in the chronic obstructive pulmonary disease (COPD) population and is associated with an increased risk of falls. This study aimed to examine postural balance during quiet standing with eyes open and functional balance [...] Read more.

Reduced balance function has been observed during balance challenging conditions in the chronic obstructive pulmonary disease (COPD) population and is associated with an increased risk of falls. This study aimed to examine postural balance during quiet standing with eyes open and functional balance in a heterogeneous group of COPD and non-COPD (control) subjects, and to identify risk factors underlying balance impairment using a large panel of methods. In COPD and control subjects, who were mostly overweight and sedentary, postural and functional balance were assessed using center-of-pressure displacement in anterior-posterior (AP) and medio-lateral (ML) directions, and the Berg Balance Scale (BBS), respectively. COPD showed 23% greater AP sway velocity (p = 0.049). The presence of oxygen therapy, fat mass, reduced neurocognitive function, and the presence of (pre)diabetes explained 71% of the variation in postural balance in COPD. Transcutaneous oxygen saturation, a history of exacerbation, and gait speed explained 83% of the variation in functional balance in COPD. Neurocognitive dysfunction was the main risk factor for postural balance impairment in the control group. This suggests that specific phenotypes of COPD patients can be identified based on their type of balance impairment. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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Review

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19 pages, 597 KiB

Open AccessReview

LABA/LAMA as First-Line Therapy for COPD: A Summary of the Evidence and Guideline Recommendations

by Marc Miravitlles, Tomotaka Kawayama and Michael Dreher

J. Clin. Med. 2022, 11(22), 6623; https://doi.org/10.3390/jcm11226623 - 08 Nov 2022

Cited by 6 | Viewed by 8685

Abstract

Inhaled bronchodilators (alone or in combination) are the cornerstone of treatment for symptomatic patients with COPD, either as initial/first-line treatment or for second-line/treatment escalation in patients who experience persistent symptoms or exacerbations on monotherapy. The Global Initiative for Chronic Obstructive Lung Disease 2022 [...] Read more.

Inhaled bronchodilators (alone or in combination) are the cornerstone of treatment for symptomatic patients with COPD, either as initial/first-line treatment or for second-line/treatment escalation in patients who experience persistent symptoms or exacerbations on monotherapy. The Global Initiative for Chronic Obstructive Lung Disease 2022 report recommends initial pharmacological treatment with a long-acting muscarinic antagonist (LAMA) or a long-acting β₂-agonist (LABA) as monotherapy for most patients, or dual bronchodilator therapy (LABA/LAMA) in patients with more severe symptoms, regardless of exacerbation history. The recommendations for LABA/LAMA are broader in the American Thoracic Society treatment guidelines, which strongly recommend LABA/LAMA combination therapy over LAMA or LABA monotherapy in patients with COPD and dyspnea or exercise intolerance. However, despite consistent guideline recommendations, real-world prescribing data indicate that LAMA and/or LABA without an inhaled corticosteroid are not the most widely prescribed therapies in COPD. This article reviews global and regional/national guideline recommendations for the use of LABA/LAMA in COPD, examines the evidence for the effectiveness and safety of LABA/LAMA versus other therapies and offers a practical guide for clinicians to help ensure appropriate use of LABA/LAMA therapy. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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7 pages, 197 KiB

Open AccessReview

The Mechanisms of Benefit of High-Flow Nasal Therapy in Stable COPD

by Massa Zantah, Aloknath Pandya, Michael R. Jacobs and Gerard J. Criner

J. Clin. Med. 2020, 9(12), 3832; https://doi.org/10.3390/jcm9123832 - 26 Nov 2020

Cited by 6 | Viewed by 2402

Abstract

High-flow nasal therapy (HFNT) is a unique system that delivers humidified, heated oxygen-enriched air via nasal cannula at high flow rates. It is a promising therapy for chronic obstructive pulmonary disease (COPD) patients. Several studies have examined the physiologic effects of this therapy [...] Read more.

High-flow nasal therapy (HFNT) is a unique system that delivers humidified, heated oxygen-enriched air via nasal cannula at high flow rates. It is a promising therapy for chronic obstructive pulmonary disease (COPD) patients. Several studies have examined the physiologic effects of this therapy in the patient population and have revealed that it improves mucociliary clearance, reduces nasopharyngeal dead space, and subsequently increases CO₂ washout. It also improves alveolar recruitment and gas exchange. These mechanisms may explain the promising results observed in recently published studies that examined the role of HFNT in stable COPD patients. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

23 pages, 2073 KiB

Open AccessReview

Data Reproducibility and Effectiveness of Bronchodilators for Improving Physical Activity in COPD Patients

by Yoshiaki Minakata and Seigo Sasaki

J. Clin. Med. 2020, 9(11), 3497; https://doi.org/10.3390/jcm9113497 - 29 Oct 2020

Cited by 4 | Viewed by 2991

Abstract

Increasing physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is an important issue, however, the effect of bronchodilators on PA is still controversial. The indicators of PA, as measured by an accelerometer, can easily fluctuate based on several factors, which [...] Read more.

Increasing physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is an important issue, however, the effect of bronchodilators on PA is still controversial. The indicators of PA, as measured by an accelerometer, can easily fluctuate based on several factors, which might cause inconsistent results. In this review, we listed the indicators of PA and the factors influencing the reproducibility of indicators of PA, and reviewed reports in which the effects of bronchodilators on PA were evaluated by an accelerometer. Then, we investigated the association between the processing of influencing factors and the effectiveness of bronchodilators for improving the PA of COPD patients. Fifteen reports were extracted using the PubMed database. In all seven reports in which adjustment was performed for at least two of four influencing factors (non-wear time, data from days with special behavior, environmental factors, and number of valid days required to obtain reproducible data), bronchodilators showed beneficial effects on PA. No adjustment was made for any of these factors in any of the four bronchodilator-ineffective reports. This suggests that the processing of influencing factors to secure reproducibility might affect the results regarding the effectiveness of bronchodilators for improving PA in COPD patients. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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20 pages, 1148 KiB

Open AccessReview

Diagnosis and Treatment of Early Chronic Obstructive Lung Disease (COPD)

by Joon Young Choi and Chin Kook Rhee

J. Clin. Med. 2020, 9(11), 3426; https://doi.org/10.3390/jcm9113426 - 26 Oct 2020

Cited by 24 | Viewed by 6852

Abstract

Chronic obstructive lung disease (COPD) is responsible for substantial rates of mortality and economic burden, and is one of the most important public-health concerns. As the disease characteristics include irreversible airway obstruction and progressive lung function decline, there has been a great deal [...] Read more.

Chronic obstructive lung disease (COPD) is responsible for substantial rates of mortality and economic burden, and is one of the most important public-health concerns. As the disease characteristics include irreversible airway obstruction and progressive lung function decline, there has been a great deal of interest in detection at the early stages of COPD during the “at risk” or undiagnosed preclinical stage to prevent the disease from progressing to the overt stage. Previous studies have used various definitions of early COPD, and the term mild COPD has also often been used. There has been a great deal of recent effort to establish a definition of early COPD, but comprehensive evaluation is still required, including identification of risk factors, various physiological and radiological tests, and clinical manifestations for diagnosis of early COPD, considering the heterogeneity of the disease. The treatment of early COPD should be considered from the perspective of prevention of disease progression and management of clinical deterioration. There has been a lack of studies on this topic as the definition of early COPD has been proposed only recently, and therefore further clinical studies are needed. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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20 pages, 1277 KiB

Open AccessReview

Comorbid Conditions in Chronic Obstructive Pulmonary Disease: Potential Therapeutic Targets for Unmet Needs

by Kazuto Matsunaga, Misa Harada, Junki Suizu, Keiji Oishi, Maki Asami-Noyama and Tsunahiko Hirano

J. Clin. Med. 2020, 9(10), 3078; https://doi.org/10.3390/jcm9103078 - 24 Sep 2020

Cited by 16 | Viewed by 7225

Abstract

The management of chronic obstructive pulmonary disease (COPD) has improved significantly due to advances in therapeutic agents, but it has also become apparent that there are issues that remain difficult to solve with the current treatment algorithm. COPD patients face a number of [...] Read more.

The management of chronic obstructive pulmonary disease (COPD) has improved significantly due to advances in therapeutic agents, but it has also become apparent that there are issues that remain difficult to solve with the current treatment algorithm. COPD patients face a number of unmet needs concerning symptoms, exacerbations, and physical inactivity. There are various risk factors and triggers for these unmet needs, which can be roughly divided into two categories. One is the usual clinical characteristics for COPD patients, and the other is specific clinical characteristics in patients with comorbid conditions, such as asthma, cardiovascular disease, and bronchiectasis. These comorbidities, which are also associated with the diversity of COPD, can cause unmet needs resistance to usual care. However, treatable conditions that are not recognized as therapeutic targets may be latent in patients with COPD. We again realized that treatable traits should be assessed and treated as early as possible. In this article, we categorize potential therapeutic targets from the viewpoint of pulmonary and systemic comorbid conditions, and address recent data concerning the pathophysiological link with COPD and the impact of intervention on comorbid conditions in order to obtain evidence that could enable us to provide personalized COPD management. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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23 pages, 935 KiB

Open AccessReview

Role of Type2 Inflammatory Biomarkers in Chronic Obstructive Pulmonary Disease

by Keiji Oishi, Kazuto Matsunaga, Toshihiro Shirai, Keita Hirai and Yasuhiro Gon

J. Clin. Med. 2020, 9(8), 2670; https://doi.org/10.3390/jcm9082670 - 18 Aug 2020

Cited by 20 | Viewed by 4772

Abstract

Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression [...] Read more.

Airway inflammation in chronic obstructive pulmonary disease (COPD) is typically thought to be driven by Type1 immune responses, while Type2 inflammation appears to be present in definite proportions in the stable state and during exacerbations. In fact, some COPD patients showed gene expression of Type2 inflammation in the airway, and this subset was associated with the inhaled corticosteroid (ICS) response. Interestingly enough, the relationship between COPD and diseases associated with Type2 inflammation from the perspective of impaired lung development is increasingly highlighted by recent epidemiologic studies on the origin of COPD. Therefore, many researchers have shown an interest in the prevalence and the role of existent Type2 biomarkers such as sputum and blood eosinophils, exhaled nitric oxide fraction, and atopy, not only in asthma but also in COPD. Although the evidence about Type2 biomarkers in COPD is inconsistent and less robust, Type2 biomarkers have shown some potential when analyzing various clinical outcomes or therapeutic response to ICS. In this article, we review the existent and emerging Type2 biomarkers with clinically higher applicability in the management of COPD. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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21 pages, 779 KiB

Open AccessReview

Current Challenges in Chronic Bronchial Infection in Patients with Chronic Obstructive Pulmonary Disease

by José Luis Lopez-Campos, Marc Miravitlles, David de la Rosa Carrillo, Rafael Cantón, Juan Jose Soler-Cataluña and Miguel Angel Martinez-Garcia

J. Clin. Med. 2020, 9(6), 1639; https://doi.org/10.3390/jcm9061639 - 28 May 2020

Cited by 20 | Viewed by 4002

Abstract

Currently, chronic obstructive pulmonary disease (COPD) patients and their physicians face a number of significant clinical challenges, one of which is the high degree of uncertainty related to chronic bronchial infection (CBI). By reviewing the current literature, several challenges can be identified, which [...] Read more.

Currently, chronic obstructive pulmonary disease (COPD) patients and their physicians face a number of significant clinical challenges, one of which is the high degree of uncertainty related to chronic bronchial infection (CBI). By reviewing the current literature, several challenges can be identified, which should be considered as goals for research. One of these is to establish the bases for identifying the biological and clinical implications of the presence of potentially pathogenic microorganisms in the airways that should be more clearly elucidated according to the COPD phenotype. Another urgent area of research is the role of long-term preventive antibiotics. Clinical trials need to be carried out with inhaled antibiotic therapy to help clarify the profile of those antibiotics. The role of inhaled corticosteroids in patients with COPD and CBI needs to be studied to instruct the clinical management of these patients. Finally, it should be explored and confirmed whether a suitable antimicrobial treatment during exacerbations may contribute to breaking the vicious circle of CBI in COPD. The present review addresses the current state of the art in these areas to provide evidence which will enable us to progressively plan better healthcare for these patients. Full article

(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: New Treatments and Future Directions)

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