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INTRODUCTION: People with HIV (PWH) have nearly twice the risk of emphysema than people without HIV. This risk, which has been associated with HIV-mediated changes in the lung immune environment and more extensive radiographic emphysema, may result in different patterns of airflow limitation on pulmonary function testing (PFT) than those traditionally used in people without HIV. METHODS: In this prospective cohort of PWH in Atlanta, Georgia, we analyzed PFT and chest computed tomography data from July 2013 through June 2018. After comparing the prevalence of PFT measures of airflow limitation for those with and without radiographic emphysema, we used binary recursive partitioning to identify PFT measures that differentiated between PWH with and without radiographic emphysema. RESULTS: Among 167 PWH who had both PFT and computed tomography data during the study period, 89 (53%) had radiographic emphysema. Those with radiographic emphysema were more likely to have airflow limitations on PFTs. Recursive partitioning identified partitions at a forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) of 0.78 and a residual volume of 116% predicted. These partitions enabled the identification of 84 (94%) PWH with radiographic emphysema, in contrast to the traditional diagnostic criteria of an FEV1/FVC ratio of 0.7, which only identified 49 (55%) of those with radiographic emphysema. CONCLUSIONS: Emphysema in PWH may have different patterns of airflow limitation on PFTs that are not adequately captured by traditional diagnostic criteria. Future studies can seek to validate these findings and determine optimal thresholds for diagnosing HIV-associated emphysema.
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Infecciones por VIH , Enfisema Pulmonar , Pruebas de Función Respiratoria , Humanos , Infecciones por VIH/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/diagnóstico por imagen , Estudios Prospectivos , Tomografía Computarizada por Rayos X , Adulto , Volumen Espiratorio Forzado , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Capacidad Vital , Georgia/epidemiologíaRESUMEN
Vanishing lung syndrome (VLS) or idiopathic giant bullous disease is a rare condition characterized by giant emphysematous bullae, classically presenting as a slowly enlarging bulla that compresses normal lung parenchyma and causes mediastinal shift, leading to increasing dyspnea and reduced exercise tolerance. Intermittent sudden worsening of symptoms may be seen because of secondary pneumothorax due to rupture of these bullae. Here we present three cases of vanishing lung syndrome in children due to tuberculosis (TB). Reports on VLS due to TB are bare minimum. In contrast to most of the published case reports, our cases had a moderate to rapid progression, bilateral extensive bullae and isoniazid which has been traditionally thought to be the causative factor was not used in one of our patients. All three are female patients arising new horizons of research regarding whether there is any sex predominance.
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Tuberculosis Pulmonar , Humanos , Femenino , Tuberculosis Pulmonar/complicaciones , Niño , Antituberculosos/uso terapéutico , Enfisema Pulmonar/complicaciones , Síndrome , Tomografía Computarizada por Rayos X , Vesícula , AdolescenteRESUMEN
INTRODUCTION: The impact of obstructive lung disease (OLD) and emphysema on lung cancer (LC) mortality in patients undergoing LC screening is controversial. METHODS: Patients with spirometry and LC diagnosed within the first three rounds of screening were selected from the National Lung Screening Trial (NLST) and from the Pamplona International Early Lung Cancer Detection Program (P-IELCAP). Medical and demographic data, tumor characteristics, comorbidities and presence of emphysema were collected. The effect of OLD and emphysema on the risk of overall survival was assessed using unadjusted and adjusted Cox models, competing risk regression analysis, and propensity score matching. RESULTS: Data from 353 patients with LC, including 291 with OLD and/or emphysema and 62 with neither, were analyzed. The median age was 67.3 years-old and 56.1% met OLD criteria, predominantly mild (1: 28.3%, 2: 65.2%). Emphysema was present in 69.4% of the patients. Patients with OLD and/or emphysema had worse survival on univariate analysis (HR: 1.40; 95% CI: 0.86-2.31; p=0.179). However, after adjusting for LC stage, age, and sex, the HR was 1.02 (95% CI: 0.61-1.70; p=0.952). Specific LC survival between both groups showed an adjusted HR of 0.90 (95% CI: 0.47-1.72; p=0.76). Propensity score matching found no statistically significant difference in overall survival (HR: 1.03; 95% CI: 0.59-1.9; p=0.929). CONCLUSION: The survival of LC patients diagnosed in the context of screening is not negatively impacted by the coexistence of mild OLD and/or emphysema.
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Detección Precoz del Cáncer , Neoplasias Pulmonares , Enfisema Pulmonar , Humanos , Masculino , Femenino , Anciano , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/complicaciones , Enfisema Pulmonar/mortalidad , Enfisema Pulmonar/complicaciones , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Puntaje de Propensión , Tamizaje Masivo , Espirometría , Comorbilidad , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Interstitial pneumonia and emphysema may complicate patients with lung cancer. However, clinical significance of trivial and mild pulmonary abnormalities remains unclear. In this study, we aimed to investigate whether trivial and mild interstitial pneumonia and emphysema, in addition to their advanced forms, impact the prognosis and lead to acute exacerbation of interstitial pneumonia (AEIP) in patients with lung cancer. METHODS: This retrospective cohort study was conducted at a tertiary hospital and included patients with lung cancer. Computed tomography images were evaluated using the interstitial lung abnormality (ILA) score for interstitial pneumonia, which included no ILA, equivocal ILA, ILA, interstitial lung disease (ILD), and the Goddard score for emphysema. Cox analyses were performed using the ILA and Goddard scores as the main explanatory variables, adjusting for multiple covariates. RESULTS: Among 1,507 patients with lung cancer, 1,033 had no ILA, 160 had equivocal ILA, 174 had ILA, and 140 had ILD. In total, 474 patients (31.5%) exhibited interstitial pneumonia and 638 (42.3%) showed emphysema. The log-rank trend test showed that survival probability was significantly better in patients with no ILA, followed by those with equivocal ILA, ILA, and ILD (P < 0.001). After adjustment, the ILA and Goddard scores remained significant variables for increased hazard ratios (HR) for mortality: no ILA (HR, 1.00: reference), equivocal ILA (HR, 1.31; 95% confidence interval [CI], 1.18-1.46; P < 0.001), ILA (HR, 1.71; 95% CI, 1.39-2.12; P < 0.001), ILD (HR, 2.24; 95% CI, 1.63-3.09; P < 0.001), and Goddard score (HR, 1.03; 95% CI, 1.01-1.06; P < 0.010). Moreover, both scores were associated with increased cause-specific HRs for AEIP. CONCLUSION: Our results revealed that approximately one-third of patients with lung cancer had interstitial pneumonia when incorporating trivial and mild cases. Because interstitial pneumonia and emphysema, ranging from trivial to severe, significantly impact mortality and AEIP in patients with lung cancer, we should identify even trivial and mild cases of these pulmonary abnormalities among patients with lung cancer in addition to the advanced ones.
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Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Enfisema Pulmonar , Tomografía Computarizada por Rayos X , Humanos , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/complicaciones , Masculino , Femenino , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Anciano , Persona de Mediana Edad , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/mortalidad , Enfisema Pulmonar/diagnóstico por imagen , Pronóstico , Progresión de la Enfermedad , Índice de Severidad de la Enfermedad , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: Emphysema is generally considered a poor prognostic factor for patients with nonsmall cell lung cancer; however, whether the poor prognosis is due to highly malignant tumors or emphysema itself remains unclear. This study was designed to determine the prognostic value of emphysema in patients with early-stage nonsmall cell lung cancer. METHODS: A total of 721 patients with clinical stage IA nonsmall cell lung cancer who underwent complete resection between April 2007 and December 2018 were retrospectively analyzed regarding clinicopathological findings and prognosis related to emphysema. RESULTS: The emphysematous and normal lung groups comprised 197 and 524 patients, respectively. Compared with the normal lung group, lymphatic invasion (23.9% vs. 14.1%, P = 0.003), vascular invasion (37.6% vs. 17.2%, P < 0.001), and pleural invasion (18.8% vs. 10.9%, P = 0.006) were observed more frequently in the emphysema group. Additionally, the 5-year overall survival rate was lower (77.1% vs. 91.4%, P < 0.001), and the cumulative incidence of other causes of death was higher in the emphysema group (14.0% vs. 3.50%, P < 0.001). Multivariable Cox regression analysis of overall survival revealed that emphysema (vs. normal lung, hazard ratio 2.02, P = 0.0052), age > 70 years (vs. < 70 years, hazard ratio 4.03, P < 0.001), and SUVmax > 1.8 (vs. ≤ 1.8, hazard ratio 2.20, P = 0.0043) were independent prognostic factors. CONCLUSIONS: Early-stage nonsmall cell lung cancer with emphysema has a tendency for the development of highly malignant tumors. Additionally, emphysema itself may have an impact on poor prognosis.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonectomía , Enfisema Pulmonar , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Femenino , Estudios Retrospectivos , Tasa de Supervivencia , Pronóstico , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Enfisema Pulmonar/cirugía , Enfisema Pulmonar/patología , Enfisema Pulmonar/complicaciones , Estadificación de Neoplasias , Enfisema/cirugía , Enfisema/patología , Enfisema/etiología , Invasividad NeoplásicaRESUMEN
BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from cachexia and malnutrition. Less is known about body composition and nutritional behaviour in patients with advanced COPD and pulmonary emphysema. METHODS: We performed a single-center prospective analysis of patients with COPD GOLD III/IV. Metabolic parameters, dietary and exercise behavior, lung function, exercise capacity and body composition by bioelectrical impedance analysis (BIA) were analyzed. Patients with severe emphysema (emphysema index [EI] >20%) were compared to patients with mild emphysema (EI ≤ 20%). RESULTS: A total of 121 patients (45.5% female, mean age 64.8 ± 8.1 years, mean FEV1 31.0 ± 8.6%, mean RV 234.7 ± 50.6%) were analyzed, of whom 14.1% were underweight. Only 5% of the patients substituted protein and only about 1/3 performed regular exercise training. BIA showed an unfavourable body composition: body fat ↑, ECM/BCM-index ↑, phase angle ↓ (5.0 ± 0.9°), cell percentage ↓, FFMI (fat-free mass index) ↓. The 94 patients with severe emphysema (mean EI 36.6 ± 8.5%) had lower body-mass-index (22.8 ± 4.3 vs. 31.1 ± 5.8 kg/m2, p < 0.001), FFMI, body weight and body fat, but did not differ significantly in the quality of body composition (e.g. phase angle). Their lipid and glucose metabolism were even better than in mild emphysema patients. CONCLUSION: The finding of significantly lower BMI but similar body composition and better metabolic status in severe emphysema patients needs further investigation. However, it should not distract from the necessity to implement dietary and exercise recommendations for advanced COPD patients.
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Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Enfisema Pulmonar/complicaciones , Impedancia Eléctrica , Estado Nutricional , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Composición Corporal , Índice de Masa CorporalRESUMEN
Chronic obstructive pulmonary disease (COPD) is caused by smoking, but only a small proportion of smokers have disease severe enough to develop COPD. COPD is not always progressive. The question then arises as to what explains the different trajectories of COPD. The role of autoimmunity and regulatory T (Treg) cells in the pathogenesis of COPD is increasingly being recognized. Nine published studies on Treg cells in the lung tissue or bronchoalveolar lavage fluid have shown that smokers with COPD have fewer Treg cells than smokers without COPD or nonsmokers. Three studies showed a positive correlation between Treg cell count and FEV1%, suggesting an important role for Treg cells in COPD progression. Treg cells can regulate immunological responses via the granzyme B (GzmB) pathway. Immunohistochemical staining for GzmB in surgically resected lungs with centrilobular emphysema showed that the relationship between the amount of GzmB+ cells and FEV1% was comparable to that between Treg cell count and FEV1% in the COPD lung, suggesting that GzmB could be a functional marker for Treg cells. The volume fraction of GzmB+ cells in the small airways, the number of alveolar GzmB+ cells, and GzmB expression measured by enzyme-linked immunosorbent assay in the lung tissue of smokers were significantly correlated with FEV1%. These results suggest that the GzmB content in lung tissue may determine the progression of COPD by acting as an effector molecule to control inflammatory process. Interventions to augment GzmB-producing immunosuppressive cells in the early stages of COPD could help prevent or delay COPD progression.
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Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Granzimas/metabolismo , Pulmón , Enfisema Pulmonar/complicaciones , Fumar/efectos adversosRESUMEN
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.
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Artritis Reumatoide , Enfisema , Enfermedades Pulmonares Intersticiales , Neoplasias Pulmonares , Enfisema Pulmonar , Fibrosis Pulmonar , Humanos , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/epidemiología , Fibrosis Pulmonar/diagnóstico , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/epidemiología , Estudios Retrospectivos , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/epidemiología , Enfisema Pulmonar/diagnóstico , Enfermedades Pulmonares Intersticiales/complicaciones , Enfisema/complicaciones , Enfisema/epidemiología , Artritis Reumatoide/complicacionesRESUMEN
BACKGROUND: Differences in disease behaviour and genotypes are described in Asian and Western interstitial lung disease (ILD) cohorts. Short leukocyte telomere length (LTL) correlates with poor outcomes in Western ILD cohorts but its significance in Asian populations is unknown. We aim to characterise the burden and clinical implications of short LTL in Singaporean ILD patients. METHODS: Patients diagnosed with ILD at Singapore General Hospital were prospectively recruited and compared against 36 healthy controls. The primary outcome was transplant-free survival. Genomic DNA from peripheral blood was extracted and LTL measured using quantitative polymerase chain reaction assay (qPCR). RESULTS: Amongst 165 patients, 37% had short LTL. There was a higher proportion of combined pulmonary fibrosis and emphysema (CPFE) patients with short LTL (n = 21, 34.4% vs n = 16, 15.4%; p < 0.001). Short LTL patients had reduced survival at 12-, 24- and 36-months and median survival of 24 months (p < 0.001) which remained significant following adjustment for smoking, GAP Stage and radiological UIP pattern (Hazard Ratio (HR), 2.74; 95%CI:1.46, 5.11; p = 0.002). They had increased respiratory-related mortality and acute exacerbation incidences. Despite similar baseline lung function, short LTL patients had a faster decline in absolute forced vital capacity (FVC) of -105.3 (95% CI: 151.4, -59.1) mL/year compared to -58.2 (95% CI: 82.9, -33.6) mL/year (p < 0.001) in normal LTL patients. CONCLUSION: Short LTL correlated with increased mortality and faster lung function decline in our Singaporean ILD cohort with a magnitude similar to that in Western ILD cohorts. Further research is needed to integrate LTL assessment into clinical practice.
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Enfermedades Pulmonares Intersticiales , Enfisema Pulmonar , Fibrosis Pulmonar , Humanos , Singapur/epidemiología , Enfermedades Pulmonares Intersticiales/etiología , Fibrosis Pulmonar/complicaciones , Enfisema Pulmonar/complicaciones , Telómero/genética , Estudios RetrospectivosAsunto(s)
Cardiopatías Congénitas , Heterotopia Nodular Periventricular , Enfisema Pulmonar , Lactante , Humanos , Heterotopia Nodular Periventricular/complicaciones , Heterotopia Nodular Periventricular/diagnóstico por imagen , Heterotopia Nodular Periventricular/genética , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/genética , Filaminas/genética , Mutación , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/genética , Imagen por Resonancia MagnéticaRESUMEN
Background: Macrophage-derived matrix metalloproteinase 12 (MMP12) can cause destruction of lung tissue structure and plays a significant role in the development and progression of chronic obstructive pulmonary disease (COPD). MTOR is a serine/threonine kinase that plays a crucial role in cell growth and metabolism. The activity of MTOR in the lung tissues of COPD patients also shows significant changes. However, it is unclear whether MTOR can regulate the development and progression of COPD by controlling MMP12. This study primarily investigates whether MTOR in macrophages can affect the expression of MMP12 and participate in the progression of COPD. Methods: We tested the changes in MTOR activity in macrophages exposed to cigarette smoke (CS) both in vivo and in vitro. Additionally, we observed the effect of MTOR on the expression of MMP12 in macrophages and on lung tissue inflammation and structural damage in mice, both in vivo and in vitro, using MTOR inhibitors or gene knockout mice. Finally, we combined inhibitor treatment with gene knockout to demonstrate that MTOR primarily mediates the expression of MMP12 through the NF-κB signaling pathway. Results: Exposure to CS can enhance MTOR activity in mouse alveolar macrophages. Inhibiting the activity of MTOR or suppressing its expression leads to increased expression of MMP12. Myeloid-specific knockout of MTOR expression can promote the occurrence of CS-induced pulmonary inflammation and emphysema in mice. Inhibiting the activity of NF-κB can eliminate the effect of MTOR on MMP12. Conclusion: Macrophage MTOR can reduce the expression of MMP12 by inhibiting NF-κB, thereby inhibiting the occurrence of COPD inflammation and destruction of lung tissue structure. Activating the activity of macrophage MTOR may be beneficial for the treatment of COPD.
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Fumar Cigarrillos , Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Serina-Treonina Quinasas TOR , Animales , Humanos , Ratones , Fumar Cigarrillos/efectos adversos , Inflamación/metabolismo , Pulmón , Macrófagos/metabolismo , Metaloproteinasa 12 de la Matriz/genética , Metaloproteinasa 12 de la Matriz/metabolismo , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Neumonía/etiología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfisema Pulmonar/complicaciones , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Productos de TabacoRESUMEN
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 (R2 = 0.25, P < 0.0001; R2 = 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.
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Enfisema , Fibrosis Pulmonar Idiopática , Enfisema Pulmonar , Humanos , Enfisema/complicaciones , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/complicaciones , Pulmón/diagnóstico por imagen , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/complicaciones , Estudios Retrospectivos , Capacidad Vital , Ensayos Clínicos como AsuntoRESUMEN
Combined pulmonary fibrosis and emphysema (CPFE) is a clinical syndrome of upper-zone-predominant emphysema on high-resolution CT and a peripheral and basal-predominant diffuse pulmonary fibrosis. Multiple occupational and inhalational exposures have been associated with CPFE. We describe a U.S. veteran, who developed CPFE after a prolonged, intense exposure to trichloroethylene as an aircraft maintenance worker. We believe that this may be another example of occupational-associated CPFE.
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Enfisema , Enfisema Pulmonar , Fibrosis Pulmonar , Tricloroetileno , Humanos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/diagnóstico por imagen , Tricloroetileno/toxicidad , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/complicaciones , Enfisema/etiología , Enfisema/complicaciones , Fibrosis , Estudios RetrospectivosRESUMEN
Rationale: Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, "pre-COPD" has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction. Objective: To determine the degree and nature of (small) airway disease in pre-COPD using microCT in a cohort of explant lobes/lungs. Methods: We collected whole lungs/lung lobes from patients with emphysematous pre-COPD (n = 10); Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I (n = 6), II (n = 6), and III/IV (n = 7) COPD; and controls (n = 10), which were analyzed using CT and microCT. The degree of emphysema and the number and morphology of small airways were compared between groups, and further correlations were investigated with physiologic measures. Airway and parenchymal pathology was also validated with histopathology. Measurements and Main Results: The numbers of transitional bronchioles and terminal bronchioles per milliliter of lung were significantly lower in pre-COPD and GOLD stages I, II, and III/IV COPD compared with controls. In addition, the number of alveolar attachments of the transitional bronchioles and terminal bronchioles was also lower in pre-COPD and all COPD groups compared with controls. We did not find any differences between the pre-COPD and COPD groups in CT or microCT measures. The percentage of emphysema on CT showed the strongest correlation with the number of small airways in the COPD groups. Histopathology showed an increase in the mean chord length and a decrease in alveolar surface density in pre-COPD and all GOLD COPD stages compared with controls. Conclusions: Lungs of patients with emphysematous pre-COPD already show fewer small airways and airway remodeling even in the absence of physiologic airway obstruction.
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Asma , Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Estudios Transversales , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/patología , Pulmón , Asma/patología , Microtomografía por Rayos XRESUMEN
Rationale: Emphysema is a chronic obstructive pulmonary disease phenotype with important prognostic implications. Identifying blood-based biomarkers of emphysema will facilitate early diagnosis and development of targeted therapies. Objectives: To discover blood omics biomarkers for chest computed tomography-quantified emphysema and develop predictive biomarker panels. Methods: Emphysema blood biomarker discovery was performed using differential gene expression, alternative splicing, and protein association analyses in a training sample of 2,370 COPDGene participants with available blood RNA sequencing, plasma proteomics, and clinical data. Internal validation was conducted in a COPDGene testing sample (n = 1,016), and external validation was done in the ECLIPSE study (n = 526). Because low body mass index (BMI) and emphysema often co-occur, we performed a mediation analysis to quantify the effect of BMI on gene and protein associations with emphysema. Elastic net models with bootstrapping were also developed in the training sample sequentially using clinical, blood cell proportions, RNA-sequencing, and proteomic biomarkers to predict quantitative emphysema. Model accuracy was assessed by the area under the receiver operating characteristic curves for subjects stratified into tertiles of emphysema severity. Measurements and Main Results: Totals of 3,829 genes, 942 isoforms, 260 exons, and 714 proteins were significantly associated with emphysema (false discovery rate, 5%) and yielded 11 biological pathways. Seventy-four percent of these genes and 62% of these proteins showed mediation by BMI. Our prediction models demonstrated reasonable predictive performance in both COPDGene and ECLIPSE. The highest-performing model used clinical, blood cell, and protein data (area under the receiver operating characteristic curve in COPDGene testing, 0.90; 95% confidence interval, 0.85-0.90). Conclusions: Blood transcriptome and proteome-wide analyses revealed key biological pathways of emphysema and enhanced the prediction of emphysema.
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Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Transcriptoma , Proteómica , Enfisema Pulmonar/genética , Enfisema Pulmonar/complicaciones , Biomarcadores , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. METHODS: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (D LCO) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. RESULTS: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. CONCLUSION: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.
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Enfisema , Fibrosis Pulmonar Idiopática , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/complicaciones , Pulmón , Fibrosis , Enfisema/complicaciones , Progresión de la Enfermedad , Estudios RetrospectivosRESUMEN
BACKGROUND Influenza infection can trigger an asthma exacerbation, which can lead to spontaneous pneumomediastinum. This is a rare condition that typically occurs after a sudden increase in intra-alveolar pressure. Pneumomediastinum is usually a benign condition that can be treated with supportive care, and it can be accompanied by subcutaneous emphysema. However, it can progress to retropharyngeal emphysema, as reported in this case. This report is of a 27-year-old patient with past medical history of well-controlled asthma presenting for acute exacerbation of asthma secondary to influenza A infection who developed pneumomediastinum, subcutaneous emphysema, and retropharyngeal emphysema. To the best of our knowledge, there is only one case in literature that has reported a similar presentation secondary to influenza A infection. CASE REPORT We report a 27-year-old woman with well-controlled asthma who presented with chest pain, shortness of breath, throat pressure, dry cough, and expiratory wheezing as an acute exacerbation of asthma secondary to influenza A infection. On chest imaging, she was found to have spontaneous pneumomediastinum, subcutaneous emphysema, and retropharyngeal emphysema. Her symptoms were resolved with supportive measures and control of asthma symptoms. CONCLUSIONS This case highlights these atypical complications of asthma exacerbations. Although these complications are typically benign and can resolve with supportive measures, severe cases can lead to acute airway compromise, pneumothorax, tension pneumomediastinum, or tension pneumopericardium. This case also shows how important it is to consider chest radiographs in any young patient with an asthma exacerbation who has symptoms or signs suggestive of extra-alveolar air.
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Asma , Gripe Humana , Enfisema Mediastínico , Enfisema Pulmonar , Enfisema Subcutáneo , Femenino , Humanos , Adulto , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Mediastínico/etiología , Gripe Humana/complicaciones , Gripe Humana/diagnóstico , Asma/complicaciones , Asma/diagnóstico , Enfisema Subcutáneo/diagnóstico por imagen , Enfisema Subcutáneo/etiología , Disnea/etiología , Enfisema Pulmonar/complicacionesRESUMEN
Combined pulmonary fibrosis and emphysema (CPFE) syndrome refers to co-occurrence of two disease processes in the lung that can be difficult to diagnose but is associated with high morbidity and mortality burden. Diagnosis of CPFE is challenging because the two diseases can counterbalance respective impairments resulting in deceivingly normal-appearing chest radiography and spirometry in a dyspneic patient. Although an international committee published the terminology and definitions of CPFE in 2022, consensus on exact diagnostic criteria and optimal management strategy is yet to be determined. Herein, we provide a narrative review summarizing the literature on CPFE from 1990 to 2022, including historical background, epidemiology, pathogenesis, clinical features, imaging and pulmonary function findings, diagnosis, prognosis, complications, and treatment. Although CPFE was initially conceived as a variant presentation of idiopathic pulmonary fibrosis, it has been recognized to occur in patients with a wide variety of interstitial lung diseases, including connective tissue disease-associated interstitial lung diseases, and hypersensitivity pneumonitis. The affected patients have a heightened risk for pulmonary hypertension and lung cancer. Clinicians need to recognize the characteristic presenting features of CPFE along with prognostic implications of this entity.
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Enfisema , Enfermedades Pulmonares Intersticiales , Enfisema Pulmonar , Fibrosis Pulmonar , Humanos , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/diagnóstico , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/diagnóstico , Pulmón/patología , Enfermedades Pulmonares Intersticiales/epidemiología , Enfisema/patología , Estudios RetrospectivosRESUMEN
INTRODUCTION: Heroin use can cause respiratory complications including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis (BD). OBJECTIVES: A general review of the literature presenting the data on the relationships between heroin consumption and bronchial complications, while underlining the difficulties of diagnosis and management. DOCUMENTARY SOURCES: Medline, 1980-2022, keywords "asthma" or "bronchospasm" or "COPD" or "bronchiectasis" and "heroin" or "opiate" or "opiates", with limits pertaining to "Title/Abstract". Concerning asthma, 26 studies were included, as were 16 for COPD and 5 for BD. RESULTS: Asthma and COPD are more prevalent among heroin addicts, who are less compliant than other patients with their treatment. The authors found a positive association between frequency of asthma exacerbations, admission to intensive care and heroin inhalation. Late diagnosis of COPD worsens the course of the disease; emphysema and BD are poor prognostic factors. CONCLUSION: Bronchial diseases in heroin users can be identified by means of respiratory function exploration and chest CT scans. These tests should be performed frequently in view of optimizing their care, which includes their weaning themselves from addictive substances.