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Respiratory Research Jan 2024No single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are...
BACKGROUND
No single pulmonary function test captures the functional effect of emphysema in idiopathic pulmonary fibrosis (IPF). Without experienced radiologists, other methods are needed to determine emphysema extent. Here, we report the development and validation of a formula to predict emphysema extent in patients with IPF and emphysema.
METHODS
The development cohort included 76 patients with combined IPF and emphysema at the Royal Brompton Hospital, London, United Kingdom. The formula was derived using stepwise regression to generate the weighted combination of pulmonary function data that fitted best with emphysema extent on high-resolution computed tomography. Test cohorts included patients from two clinical trials (n = 455 [n = 174 with emphysema]; NCT00047645, NCT00075998) and a real-world cohort from the Royal Brompton Hospital (n = 191 [n = 110 with emphysema]). The formula is only applicable for patients with IPF and concomitant emphysema and accordingly was not used to detect the presence or absence of emphysema.
RESULTS
The formula was: predicted emphysema extent = 12.67 + (0.92 x percent predicted forced vital capacity) - (0.65 x percent predicted forced expiratory volume in 1 second) - (0.52 x percent predicted carbon monoxide diffusing capacity). A significant relationship between the formula and observed emphysema extent was found in both cohorts (R = 0.25, P < 0.0001; R = 0.47, P < 0.0001, respectively). In both, the formula better predicted observed emphysema extent versus individual pulmonary function tests. A 15% emphysema extent threshold, calculated using the formula, identified a significant difference in absolute changes from baseline in forced vital capacity at Week 48 in patients with baseline-predicted emphysema extent < 15% versus ≥ 15% (P = 0.0105).
CONCLUSION
The formula, designed for use in patients with IPF and emphysema, demonstrated enhanced ability to predict emphysema extent versus individual pulmonary function tests.
TRIAL REGISTRATION
NCT00047645; NCT00075998.
Topics: Humans; Emphysema; Idiopathic Pulmonary Fibrosis; Lung; Pulmonary Emphysema; Retrospective Studies; Vital Capacity; Clinical Trials as Topic
PubMed: 38238788
DOI: 10.1186/s12931-023-02589-x -
American Journal of Respiratory and... Aug 2023
Topics: Humans; Cross-Sectional Studies; Pulmonary Emphysema; Pulmonary Disease, Chronic Obstructive; Emphysema; Lung
PubMed: 37450936
DOI: 10.1164/rccm.202307-1198ED -
Experimental & Molecular Medicine Oct 2023The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in...
The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema.
Topics: Humans; Anti-Bacterial Agents; Dysbiosis; Interleukin-6; Pulmonary Emphysema; Inflammation; Emphysema; Autophagy
PubMed: 37779147
DOI: 10.1038/s12276-023-01099-6 -
European Respiratory Review : An... Mar 2021In recent years, many bronchoscopic techniques have been developed in chronic obstructive airway inflammatory diseases, including asthma, COPD and emphysema. The main...
In recent years, many bronchoscopic techniques have been developed in chronic obstructive airway inflammatory diseases, including asthma, COPD and emphysema. The main techniques with available data from randomised controlled trials are: 1) bronchial thermoplasty in asthma; 2) valves, coils and thermal vapor ablation in emphysema; and 3) targeted lung denervation in COPD. The objectives of this article are to describe the levels of evidence for efficacy and safety, long-term follow-up results beyond 1 year, and current recommendations for clinical practice from international guidelines for each technique.
Topics: Asthma; Bronchoscopy; Emphysema; Humans; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema
PubMed: 33650526
DOI: 10.1183/16000617.0029-2020 -
Respiratory Care Sep 2017Dynamic hyperinflation is a common cause of dyspnea and functional limitation in patients with emphysema. Dynamic hyperinflation occurs in individuals with air-flow... (Review)
Review
Dynamic hyperinflation is a common cause of dyspnea and functional limitation in patients with emphysema. Dynamic hyperinflation occurs in individuals with air-flow limitation when expiratory time is decreased during periods of relative tachypnea (such as during exercise or agitation, for example). In this setting, patients with emphysema develop lung hyperinflation, impairment of inspiratory respiratory muscles, and an increase in work of breathing. The associated decrease in inspiratory capacity results in the stimulation of several receptors, including chemoreceptors and pulmonary receptors, which signal the brain to increase tidal volume. The inability of the respiratory system to respond to signals of increased demand (eg, by enlarging tidal volume and increasing inspiratory flow) results in a dissociation between afferent and efferent signaling thereby intensifying breathing discomfort, or what clinicians term dyspnea. A thorough understanding of the physiology of dyspnea and pathophysiology of dynamic hyperinflation informs the interventions used to mitigate sensations of dyspnea and the physiologic effects of dynamic hyperinflation, respectively. Pharmacotherapy, pulmonary rehabilitation, breathing techniques, positive airway pressure, and lung volume reduction are well-studied interventions that target pathways to dyspnea in patients with dynamic hyperinflation.
Topics: Dyspnea; Humans; Inhalation; Inspiratory Capacity; Lung; Pulmonary Emphysema; Pulmonary Ventilation; Respiratory Physiological Phenomena
PubMed: 28655742
DOI: 10.4187/respcare.05198 -
International Journal of Chronic... 2017It is increasingly acknowledged that delays in the diagnosis of chronic inflammatory lung conditions have hampered our understanding of pathogenesis and thus our ability... (Review)
Review
It is increasingly acknowledged that delays in the diagnosis of chronic inflammatory lung conditions have hampered our understanding of pathogenesis and thus our ability to design efficacious therapies. This is particularly true for COPD, where most patients are diagnosed with moderate-to-severe airflow obstruction and little is known about the inflammatory processes present in early disease. There is great interest in developing screening tests that can identify those most at risk of developing COPD before airflow obstruction has developed for the purpose of research and clinical care. Landmark pathology studies have suggested that damage to the small airways precedes the development of airflow obstruction and emphysema and, thus, presents an opportunity to identify those at risk of COPD. However, despite a number of physiological tests being available to assess small airways function, none have been adopted into routine care in COPD. The reasons that tests of small airways have not been utilized widely include variability in test results and a lack of validated reference ranges from which to compare results for some methodologies. Furthermore, population studies have not consistently demonstrated their ability to diagnose disease. However, the landscape may be changing. As the equipment that delivers tests of small airways become more widely available, reference ranges are emerging and newer methodologies specifically seek to address variability and difficulty in test performance. Moreover, there is evidence that while tests of small airways may not be helpful across the full range of established disease severity, there may be specific groups (particularly those with early disease) where they might be informative. In this review, commonly utilized tests of small airways are critically appraised to highlight why these tests may be important, how they can be used and what knowledge gaps remain for their use in COPD.
Topics: Airway Obstruction; Disease Progression; Humans; Lung; Predictive Value of Tests; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Respiratory Function Tests; Risk Factors
PubMed: 28848335
DOI: 10.2147/COPD.S138540 -
International Journal of Chronic... 2015As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are available to achieve lung volume reduction in patients with severe... (Review)
Review
As well as lung volume reduction surgery, different minimally invasive endoscopic techniques are available to achieve lung volume reduction in patients with severe emphysema and significant hyperinflation. Lung function parameters and comorbidities of the patient, as well as the extent and distribution of the emphysema are factors to be considered when choosing the patient and the intervention. Endoscopic bronchial valve placement with complete occlusion of one lobe in patients with heterogeneous emphysema is the preferred technique because of its reversibility. The presence of high interlobar collateral ventilation will hinder successful treatment; therefore, endoscopic coil placement, polymeric lung volume reduction, or bronchoscopic thermal vapor ablation as well as lung volume reduction surgery can be used for treating patients with incomplete fissures. The effect of endoscopic lung volume reduction in patients with a homogeneous distribution of emphysema is still unclear and this subgroup should be treated only in clinical trials. Precise patient selection is necessary for interventions and to improve the outcome and reduce the risk and possible complications. Therefore, the patients should be discussed in a multidisciplinary approach prior to determining the most appropriate treatment for lung volume reduction.
Topics: Bronchoscopy; Humans; Outcome Assessment, Health Care; Patient Selection; Pneumonectomy; Pulmonary Emphysema; Pulmonary Ventilation; Risk Adjustment
PubMed: 26504379
DOI: 10.2147/COPD.S63473 -
International Journal of Chronic... 2021Disease heterogeneity in idiopathic pulmonary fibrosis (IPF) often complicates the systematic study of disease, management of patients and clinical investigations.
BACKGROUND
Disease heterogeneity in idiopathic pulmonary fibrosis (IPF) often complicates the systematic study of disease, management of patients and clinical investigations.
OBJECTIVE
To describe combined pulmonary fibrosis emphysema (CPFE) phenotype in a rural Appalachian IPF cohort with the highest smoking rates in the United States.
METHODS
CPFE patients (n = 60) in a developed IPF cohort (n = 153) were characterized. Groups (CPFE vs IPF without emphysema) were categorized based on the predominant HRCT patterns of UIP (n = 109). Demographics, clinical variables, and treatment details were recorded. Kaplan-Meier survival and multivariate logistic regression analysis were performed.
RESULTS
The prevalence of CPFE in our IPF cohort was 45% (n = 49). The CPFE group was younger (73.9 vs 78.2), had a more extensive smoking history (93.9% vs 53.3%) with greater mean smoking pack years (49.09 vs 15.39) and had lower percentage predicted DL on presentation (38.35 vs 51.09) compared to IPF without emphysema group. Both groups shared equivalent higher burden of comorbidities, including pulmonary hypertension (PH) (46.9% vs 33.3%). One-fifth of patients were prescribed antifibrotics and only a subset (5%) of patients underwent lung transplantation. There was a non-significant trend towards reduced survival in CPFE (p = 0.076). Smoking status and DL predicted CPFE in our cohort. Body mass index (BMI), PH, and pirfenidone use were significant predictors of mortality.
CONCLUSION
CPFE was highly prevalent in our rural IPF cohort. In contrast to previous studies, CPFE group was older and had higher female (approx. 30%) occurrence. A greater exposure to cigarette smoke and reduced DL at diagnosis predicted CPFE. Lower BMI and PH predicted higher mortality whereas use of pirfenidone improved survival in our cohort. This study highlights a complex interaction of cigarette smoking, advanced fibrosis of UIP, PH and potential utility of antifibrotic agents in CPFE phenotype. Substantial burden of comorbidities, older age, and the limited utilization of advanced therapeutics in the cohort emphasize the challenges faced by rural Appalachian patients.
Topics: Aged; Cigarette Smoking; Emphysema; Female; Fibrosis; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Retrospective Studies
PubMed: 34188464
DOI: 10.2147/COPD.S307192 -
International Journal of Chronic... 2017COPD is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality. The major risk factor for COPD development is cigarette smoke, and... (Review)
Review
COPD is the most frequent chronic respiratory disease and a leading cause of morbidity and mortality. The major risk factor for COPD development is cigarette smoke, and the most efficient treatment for COPD is smoking cessation. However, even after smoking cessation, inflammation, apoptosis, and oxidative stress may persist and continue contributing to disease progression. Although current therapies for COPD (primarily based on anti-inflammatory agents) contribute to the reduction of airway obstruction and minimize COPD exacerbations, none can avoid disease progression or reduce mortality. Within this context, recent advances in mesenchymal stromal cell (MSC) therapy have made this approach a strong candidate for clinical use in the treatment of several pulmonary diseases. MSCs can be readily harvested from diverse tissues and expanded with high efficiency, and have strong immunosuppressive properties. Preclinical studies have demonstrated encouraging outcomes of MSCs therapy for lung disorders, including emphysema. These findings instigated research groups to assess the impact of MSCs in human COPD/emphysema, but clinical results have fallen short of expectations. However, MSCs have demonstrated a good adjuvant role in the clinical scenario. Trials that used MSCs combined with another, primary treatment (eg, endobronchial valves) found that patients derived greater benefit in pulmonary function tests and/or quality of life reports, as well as reductions in systemic markers of inflammation. The present review summarizes and describes the more recent preclinical studies that have been published about MSC therapy for COPD/emphysema and discusses what has already been applied about MSCs treatment in COPD patients in the clinical setting.
Topics: Airway Remodeling; Animals; Disease Models, Animal; Humans; Lung; Mesenchymal Stem Cell Transplantation; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Recovery of Function; Regeneration; Translational Research, Biomedical; Treatment Outcome
PubMed: 29081655
DOI: 10.2147/COPD.S146671 -
PloS One 2024Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of...
OBJECTIVE
Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of this study was to examine the effect of CPFE on lung cancer risk and lung cancer-related mortality in patients with rheumatoid arthritis (RA).
METHODS
We conducted a multicenter retrospective cohort study of patients newly diagnosed with lung cancer at five community hospitals between June 2006 and December 2021. Patients were followed until lung cancer-related death, other-cause death, loss to follow-up, or the end of the study. We used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis.
RESULTS
A total of 563 patients with biopsy-proven lung cancer were included (82 RA patients and 481 non-RA patients). The prevalence of CPFE was higher in RA patients than in non-RA patients (40.2% vs.10.0%) at lung cancer diagnosis. During follow-up, the crude incidence rate of lung cancer-related death was 0.29 and 0.10 per patient-year (PY) in RA and non-RA patients, and 0.32 and 0.07 per PY in patients with CPFE and patients without ILD or emphysema, respectively. The estimated death probability at 5 years differed between RA and non-RA patients (66% vs. 32%, p<0.001) and between patients with CPFE and patients without ILD or emphysema (71% vs. 24%, p<0.001). In addition to clinical cancer stage and no surgery within 1 month, RA and CPFE were identified as independent predictive factors for increased lung cancer-related mortality (RA: adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.65-4.76; CPFE: adjusted HR 2.01; 95% CI 1.24-3.23).
CONCLUSIONS
RA patients with lung cancer had a higher prevalence of CPFE and increased cancer-related mortality compared with non-RA patients. Close monitoring and optimal treatment strategies tailored to RA patients with CPFE are important to improve the poor prognosis of lung cancer.
Topics: Humans; Pulmonary Fibrosis; Lung Neoplasms; Retrospective Studies; Pulmonary Emphysema; Lung Diseases, Interstitial; Emphysema; Arthritis, Rheumatoid
PubMed: 38412181
DOI: 10.1371/journal.pone.0298573