scispace - formally typeset
Search or ask a question

Showing papers in "BMC Pulmonary Medicine in 2019"


Journal ArticleDOI
TL;DR: Some sampling strategies of cryobiopsy seem to be associated with a higher diagnostic yield and a favorable risk/benefit ratio: sampling at least two samples in different sites, using either the 2.4 mm or 1.9‬mm probe.
Abstract: Standardization of trans-bronchial lung cryobiopsy in diffuse parenchymal lung diseases is imminent; however, the majority of published series on cryobiopsy include a limited number of patients and are characterized by several differences in procedural technical details. This is an observational, retrospective cohort study. Aim of the study was to suggest some sampling strategies related to transbronchial cryobiopsy in the diagnostic work-up of patients with diffuse parenchymal lung diseases. Six hundred ninety-nine patients with suspected diffuse parenchymal lung disease were recruited. A specific pathological diagnosis was achieved in 614/699 cases (87.8%) and a multidisciplinary diagnosis was obtained in 630/699 cases (90.1%). Diagnostic yield was significantly influenced by the number of samples taken (1 vs ≥ 2 biopsies, p < 0.005). In 60.4% of patients, biopsies were taken from one site and in 39.6% from different sites (in the same lobe or in two different lobes), with a significant increase in diagnostic yield, specifically in patients with fibrotic lung diseases (65.5% vs 93.4%, p < 0.0001). The 2.4 mm or 1.9 mm probes were used, with no differences in terms of diagnostic yield. Regarding safety, pneumothorax occurred in 19.2% and was influenced by baseline lung function; in all patients Fogarty balloon has been used and severe haemorrhage occurred in 0.7% of cases. Three patients (0.4% of cases) died within 30 days after the procedure. We propose some sampling strategies of cryobiopsy which seem to be associated with a higher diagnostic yield and a favorable risk/benefit ratio: sampling at least two samples in different sites, using either the 2.4 mm or the 1.9 mm probe, intubating the patients and using bronchial blockers/catheters.

128 citations


Journal ArticleDOI
TL;DR: Metagenomic next-generation sequencing is a promising technique to detect co-pathogens in mixed pulmonary infection, with potential benefits in speed and sensitivity and application of mNGS improved the diagnosis of pulmonary fungal infections.
Abstract: Metagenomic next-generation sequencing (mNGS) is emerging as a promising technique for pathogens detection. However, reports on the application of mNGS in mixed pulmonary infection remain scarce. From July 2018 to March 2019, 55 cases were enrolled in this retrospective analysis. Cases were classified into mixed pulmonary infection (36 [65.5%]) and non-mixed pulmonary infection (19 [34.5%]) according to primary diagnoses. The performances of mNGS and conventional test on mixed pulmonary infection diagnosis and pathogen identification were compared. The sensitivity of mNGS in mixed pulmonary infection diagnosis was much higher than that of conventional test (97.2% vs 13.9%; P < 0.01), but the specificity was the opposite (63.2% vs 94.7%; P = 0.07). The positive predictive value of mNGS was 83.3% (95% CI, 68.0–92.5%), and the negative predictive value was 92.3% (95% CI, 62.1–99.6%). A total of 5 (9.1%) cases were identified as mixed pulmonary infection by both conventional tests and mNGS, however, the pathogens identification results were consistent between these two methods in only 1 (1.8%) case. In summary, the pathogens detected by mNGS in 3 (5.5%) cases were consistent with those by conventional test, and only 1 (1.8%) case was mixed pulmonary infection. According to our data, mNGS had a broader spectrum for pathogen detection than conventional tests. In particular, application of mNGS improved the diagnosis of pulmonary fungal infections. Within the 55 cases, mNGS detected and identified fungi in 31 (56.4%) cases, of which only 10 (18.2%) cases were positive for the same fungi by conventional test. The most common pathogen detected by mNGS was Human cytomegalovirus in our study, which was identified in 19 (34.5%) cases of mixed pulmonary infection. Human cytomegalovirus and Pneumocystis jirovecii, which were detected in 7 (12.7%) cases, were the most common co-pathogens in the group of mixed pulmonary infection. mNGS is a promising technique to detect co-pathogens in mixed pulmonary infection, with potential benefits in speed and sensitivity. (retrospectively registered): ChiCTR1900023727. Registrated 9 JUNE 2019.

104 citations


Journal ArticleDOI
TL;DR: RAB implementation in community and academic centers is safe and feasible, with an initial diagnostic yield of 69.1–77% in patients with lung lesions that require diagnostic bronchoscopy.
Abstract: The Robotic Endoscopic System (Auris Health, Inc., Redwood City, CA) has the potential to overcome several limitations of contemporary guided-bronchoscopic technologies for the diagnosis of lung lesions. Our objective is to report on the initial post-marketing feasibility, safety and diagnostic yield of this technology. We retrospectively reviewed data on consecutive cases in which robot-assisted bronchoscopy was used to sample lung lesions at four centers in the US (academic and community) from June 15th, 2018 to December 15th, 2018. One hundred and sixty-seven lesions in 165 patients were included in the analysis, with an average follow-up of 185 ± 55 days. The average size of target lesions was 25.0 ± 15.0 mm. Seventy-one percent were located in the peripheral third of the lung. Pneumothorax and airway bleeding occurred in 3.6 and 2.4% cases, respectively. Navigation was successful in 88.6% of cases. Tissue samples were successfully obtained in 98.8%. The diagnostic yield estimates ranged from 69.1 to 77% assuming the cases of biopsy-proven inflammation without any follow-up information (N = 13) were non-diagnostic and diagnostic, respectively. The yield was 81.5, 71.7 and 26.9% for concentric, eccentric and absent r-EBUS views, respectively. Diagnostic yield was not affected by lesion size, density, lobar location or centrality. RAB implementation in community and academic centers is safe and feasible, with an initial diagnostic yield of 69.1–77% in patients with lung lesions that require diagnostic bronchoscopy. Comparative trials with the existing bronchoscopic technologies are needed to determine cost-effectiveness of this technology.

97 citations


Journal ArticleDOI
TL;DR: The incidence and prevalence of NTM infection in Korea increased rapidly from 2003 to 2016 and were higher in women and the elderly, and the mortality rate in the population with N TM infection was higher than that in the general population.
Abstract: Epidemiologic characteristics of nontuberculous mycobacterial (NTM) disease remain largely unknown. The objective of this study was to evaluate incidence, prevalence, and mortality of NTM infection in a large nationwide population-based cohort in Korea. Data of the National Health Insurance Service database, an extensive health-related database including most Korean residents, were used. Adults with a primary diagnosis of NTM as determined by International Classification of Disease-Tenth Revision coding (A31) were identified between 2003 and 2016. Incidence, prevalence, and mortality of NTM infection were analyzed. A total of 46,194 individuals had a primary diagnosis of NTM infection. Their mean age was 55.8 years. Of these subjects, 61.1% were females. Annual age-adjusted incidence and prevalence of NTM infection tended to increase rapidly from 2003 to 2016. Age-adjusted incidence and prevalence was 17.9 and 33.3 per 100,000 population in 2016. The incidence and prevalence were higher in females and the elderly. The 5-year mortality rate in the population with NTM infection was 17.8%. The standardized mortality ratio of patients with NTM infection to the general population was 2.16 (95% confidence interval: 2.10 to 2.22). This large population-based study showed that the incidence and prevalence of NTM infection in Korea increased rapidly from 2003 to 2016. They were higher in women and the elderly. The mortality rate in the population with NTM infection was higher than that in the general population.

70 citations


Journal ArticleDOI
TL;DR: Hyperoxia would lead to higher mortality in critically ill patients especially in the patients with cardiac arrest and ELS.
Abstract: Studies investigating the role of hyperoxia in critically ill patients have reported conflicting results. We did this analysis to reveal the effect of hyperoxia in the patients admitted to the intensive care unit (ICU). Electronic databases were searched for all the studies exploring the role of hyperoxia in adult patients admitted to ICU. The primary outcome was mortality. Random-effect model was used for quantitative synthesis of the adjusted odds ratio (aOR). We identified 24 trials in our final analysis. Statistical heterogeneity was found between hyperoxia and normoxia groups in patients with mechanical ventilation (I2 = 92%, P < 0.01), cardiac arrest(I2 = 63%, P = 0.01), traumatic brain injury (I2 = 85%, P < 0.01) and post cardiac surgery (I2 = 80%, P = 0.03). Compared with normoxia, hyperoxia was associated with higher mortality in overall patients (OR 1.22, 95% CI 1.12~1.33), as well as in the subgroups of cardiac arrest (OR 1.30, 95% CI 1.08~1.57) and extracorporeal life support (ELS) (OR 1.44, 95% CI 1.03~2.02). Hyperoxia would lead to higher mortality in critically ill patients especially in the patients with cardiac arrest and ELS.

67 citations


Journal ArticleDOI
TL;DR: Findings from a large, nationally representative survey suggest increased odds of asthma among never combustible smoking e-cigarette users, providing a strong rationale to support future longitudinal studies of pulmonary health in young e- cigarette-using adults.
Abstract: E-cigarette use prevalence has grown rapidly in the US. Despite the popularity of these products, few acute exposure toxicity studies exist, and studies on long-term pulmonary health effects are limited. E-cigarette users who are never combustible cigarette smokers (sole users) constitute a unique group of young adults that may be at increased risk of bronchial hyperreactivity and development of asthma. Given the public health concern about the potential pulmonary health effects of sole e-cigarette use, we aimed to examine the association between e-cigarette use and asthma among never combustible cigarette smokers. We pooled 2016 and 2017 data of the Behavioral Risk Factor Surveillance System (BRFSS), a large, cross-sectional telephone survey of adults aged 18 years and older in the U.S. We included 402,822 participants without any history of combustible cigarette smoking (defined as lifetime smoking < 100 cigarettes) and with complete self-reported information on key variables. Current e-cigarette use, further classified as daily or occasional use, was the primary exposure. The main outcome, asthma, was defined as self-reported history of asthma. We assess the relationship of sole e-cigarette use with asthma using multivariable logistic regression adjusting for age, sex, race, income, level of education and body mass index. Of 402,822 never combustible cigarette smokers, there were 3103 (0.8%) current e-cigarette users and 34,074 (8.5%) with asthma. The median age group of current e-cigarette users was 18–24 years. Current e-cigarette use was associated with 39% higher odds of self-reported asthma compared to never e-cigarette users (Odds Ratio [OR], 1.39; 95% confidence interval: 1.15, 1.68). There was a graded increased odds of having asthma with increase of e-cigarette use intensity. The odds ratio of self-reported asthma increased from 1.31 (95% confidence interval: 1.05, 1.62) in occasional users to 1.73 (95% confidence interval: 1.21, 2.48) in daily e-cigarette users, compared to never e-cigarette users. Our findings from a large, nationally representative survey suggest increased odds of asthma among never combustible smoking e-cigarette users. This may have potential public health implications, providing a strong rationale to support future longitudinal studies of pulmonary health in young e-cigarette-using adults.

64 citations


Journal ArticleDOI
TL;DR: Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone.
Abstract: Differentiating bacterial from viral pneumonia is important for guiding targeted management and judicious use of antibiotics. We assessed if clinical characteristics and blood inflammatory biomarkers could be used to distinguish bacterial from viral pneumonia. Western Australian children (≤17 years) hospitalized with radiologically-confirmed community-acquired pneumonia were recruited and clinical symptoms and management data were collected. C-reactive protein (CRP), white cell counts (WCC) and absolute neutrophil counts (ANC) were measured as part of routine care. Clinical characteristics and biomarker levels were compared between cases with definite bacterial pneumonia (clinical empyema and/or bacteria detected in blood or pleural fluid), presumed viral pneumonia (presence of ≥1 virus in nasopharyngeal swab without criteria for definite bacterial pneumonia), and other pneumonia cases (pneumonia in the absence of criteria for either definite bacterial or presumed viral pneumonia). The area-under-curve (AUC) of the receiver operating characteristic (ROC) curve for varying biomarker levels were used to characterise their utility for discriminating definite bacterial from presumed viral pneumonia. For biomarkers with AUC > 0.8 (fair discriminator), Youden index was measured to determine the optimal cut-off threshold, and sensitivity, specificity, predictive values (positive and negative) were calculated. We investigated whether better discrimination could be achieved by combining biomarker values with the presence/absence of symptoms. From May 2015 to October 2017, 230 pneumonia cases were enrolled: 30 with definite bacterial pneumonia, 118 with presumed viral pneumonia and 82 other pneumonia cases. Differences in clinical signs and symptoms across the groups were noted; more definite bacterial pneumonia cases required intravenous fluid and oxygen supplementation than presumed viral or other pneumonia cases. CRP, WCC and ANC were substantially higher in definite bacterial cases. For a CRP threshold of 72 mg/L, the AUC of ROC was 0.82 for discriminating definite bacterial pneumonia from presumed viral pneumonia. Combining the CRP with either the presence of fever (≥38οC) or the absence of rhinorrhea improved the discrimination. Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone. Further studies are required to explore combination of biomarkers and symptoms for use as definitive diagnostic tool.

60 citations


Journal ArticleDOI
TL;DR: High proportions of TB patients were malnourished and even a very distal reason for malnutrition in the community became a proximal cause for TB patients.
Abstract: Each year, more than 13.7 million people became an active case of tuberculosis and more than 1.5 million cases of TB patient will die. The association between TB and malnutrition is bi-directional, TB leads the patient to malnutrition, and malnutrition increases the risk of developing active TB by 6 to 10 times. Improving the nutrition of individual greatly reduces tuberculosis. The aims of this study were to assess the nutritional status and determinants of underweight among TB patients. A comparative cross-sectional study design was implemented. The sample size was calculated using 95% CI, 90% power, the prevalence of malnutrition in TB patients 50%, TB patients to TB free resident ratio of 3, the design effect of 2 and a 5% non-response rate. Systematic random sampling was used to select TB patients and simple random sampling technique was used to select TB free residents. The data were collected from July 2015–May 2018. The data were collected by interviewing the patient, measuring anthropometric indicators and collecting the stool and blood samples. The data were entered into the computer using Epi-info software and analyzed using SPSS software. Descriptive statistics were used to find the proportion of malnutrition. Binary logistic regression was used to identify the determinants of malnutrition. A total of 5045 study participants (1681 TB patients and 3364 TB free residents) were included giving for the response rate of 93.1%. The prevalence of underweight among TB patients was 57.17% (95% CI: 54.80, − 59.54%) and 88.52% of TB patients were anemic. The prevalence of malnutrition (underweight) among TB free residents was 23.37% (95% CI: 21.93–24.80). The nutritional status of TB patients was determined by site of infection AOR: 0.68 [0.49–0.94], sex of the patient AOR: 0.39 [0.25–0.56], residence AOR: 3.84 [2.74–5.54], intestinal parasite infection AOR: 7 [5.2–9.95], problematic alcohol use AOR: 1.52 [1.17–2.13]. High proportions of TB patients were malnourished. TB patients were highly susceptible to malnutrition and even a very distal reason for malnutrition in the community became a proximal cause for TB patients.

50 citations


Journal ArticleDOI
TL;DR: The current literature suggests that the economic burden of bronchiectasis in society is significant, but the true economic burden is likely to be underestimated because most studies were retrospective, used ICD-9-CM coding to identify patients, and often ignored outpatient burden and cost.
Abstract: The increasing prevalence and recognition of bronchiectasis in clinical practice necessitates a better understanding of the economic disease burden to improve the management and achieve better clinical and economic outcomes. This study aimed to assess the economic burden of bronchiectasis based on a review of published literature. A systematic literature review was conducted using MEDLINE, Embase, EconLit and Cochrane databases to identify publications (1 January 2001 to 31 December 2016) on the economic burden of bronchiectasis in adults. A total of 26 publications were identified that reported resource use and costs associated with management of bronchiectasis. Two US studies reported annual incremental costs of bronchiectasis versus matched controls of US$5681 and US$2319 per patient. Twenty-four studies reported on hospitalization rates or duration of hospitalization for patients with bronchiectasis. Mean annual hospitalization rates per patient, reported in six studies, ranged from 0.3–1.3, while mean annual age-adjusted hospitalization rates, reported in four studies, ranged from 1.8–25.7 per 100,000 population. The average duration of hospitalization, reported in 12 studies, ranged from 2 to 17 days. Eight publications reported management costs of bronchiectasis. Total annual management costs of €3515 and €4672 per patient were reported in two Spanish studies. Two US studies reported total costs of approximately US$26,000 in patients without exacerbations, increasing to US$36,00–37,000 in patients with exacerbations. Similarly, a Spanish study reported higher total annual costs for patients with > 2 exacerbations per year (€7520) compared with those without exacerbations (€3892). P. aeruginosa infection increased management costs by US$31,551 to US$56,499, as reported in two US studies, with hospitalization being the main cost driver. The current literature suggests that the economic burden of bronchiectasis in society is significant. Hospitalization costs are the major driver behind these costs, especially in patients with frequent exacerbations. However, the true economic burden of bronchiectasis is likely to be underestimated because most studies were retrospective, used ICD-9-CM coding to identify patients, and often ignored outpatient burden and cost. We present a conceptual framework to facilitate a more comprehensive assessment of the true burden of bronchiectasis for individuals, healthcare systems and society.

50 citations


Journal ArticleDOI
TL;DR: A meta-analysis based on sufficient evidence demonstrated by TSA suggests that LDCT screening is superiority over usual care in lung cancer survival.
Abstract: The Nelson mortality results were presented in September 2018 Four other randomized control trials (RCTs) were also reported the latest mortality outcomes in 2018 and 2019 We therefore conducted a meta-analysis to update the evidence and investigate the benefits and harms of low-dose computed tomography (LDCT) in lung cancer screening Detailed electronic database searches were performed to identify reports of RCTs that comparing LDCT to any other type of lung cancer screening Pooled risk ratios (RRs) were calculated using random effects models We identified nine RCTs (n = 97,244 participants) In pooled analyses LDCT reduced lung cancer mortality (RR 083, 95% CI 076–090, I2 = 1%) but had no effect on all-cause mortality (RR 095, 95% CI 090–100) Trial sequential analysis (TSA) confirmed the results of our meta-analysis Subgroup defined by high quality trials benefitted from LDCT screening in reducing lung cancer mortality (RR 082, 95% CI 073–091, I2 = 7%), whereas no benefit observed in other low quality RCTs LDCT was associated with detection of a significantly higher number of early stage lung cancers than the control No significant difference (RR 064, 95% CI 030–133) was found in mortality after invasive procedures between two groups In meta-analysis based on sufficient evidence demonstrated by TSA suggests that LDCT screening is superiority over usual care in lung cancer survival The benefit of LDCT is expected to be heavily influenced by the risk of lung cancer in the different target group (smoking status, Asian) being screened

49 citations


Journal ArticleDOI
TL;DR: Ligustrazin blocked PQ-induced PI3K/Akt/mTOR and Hh signalling and reduced oxidative stress via increasing miR-193a expression and autophagy, all of which reduced pulmonary fibrosis.
Abstract: Reactive oxygen species (ROS) levels largely determine pulmonary fibrosis. Antioxidants have been found to ameliorate lung fibrosis after long-term paraquat (PQ) exposure. The effects of antioxidants, however, on the signalling pathways involved in PQ-induced lung fibrosis have not yet been investigated sufficiently. Here, we examined the impacts of ligustrazin on lung fibrosis, in particular ROS-related autophagy and pro-fibrotic signalling pathways, using a murine model of PQ-induced lung fibrosis. We explored the effects of microRNA-193 (miR-193a) on Hedgehog (Hh) and PI3K/Akt/mTOR signalling and oxidative stress in lung tissues. Levels of miR-193a, protein kinase B (Akt), phosphoinositide 3-Kinase (PI3K), ceclin1, mammalian target of rapamycin (mTOR), sonic hedgehog (SHH), myosin-like Bcl2 interacting protein (LC3), smoothened (Smo), and glioma-associated oncogene-1 (Gli-1) mRNAs were determined with quantitative real-time PCR. Protein levels of PI3K, p-mTOR, p-Akt, SHH, beclin1, gGli-1, LC3, smo, transforming growth factor-β1 (TGF-β1), mothers against DPP homologue-2 (Smad2), connective tissue growth factor (CTGF), collagen I, collagen III, α-smooth muscle actin (α-SMA) nuclear factor erythroid 2p45-related factor-2 (Nrf2), and p-Smad2 were detected by western blotting. In addition, α-SMA, malondialdehyde, ROS, superoxide dismutase (SOD), oxidised and reduced glutathione, hydroxyproline, and overall collagen levels were identified in lung tissues using immunohistochemistry. Long-term PQ exposure blocked miR-193a expression, reduced PI3K/Akt/mTOR signalling, increased oxidative stress, inhibited autophagy, increased Hh signalling, and facilitated the formation of pulmonary fibrosis. Ligustrazin blocked PI3K/Akt/mTOR and Hh signalling as well as reduced oxidative stress via increasing miR-193a expression and autophagy, all of which reduced pulmonary fibrosis. These effects of ligustrazin were accompanied by reduced TGF-β1, CTGF, and Collagen I and III expression. Ligustrazin blocked PQ-induced PI3K/Akt/mTOR and Hh signalling by increasing miR-193a expression, thereby attenuating PQ-induced lung fibrosis.

Journal ArticleDOI
TL;DR: RAB may be beneficial for patients with peripheral lung lesions that require biopsy prior to surgical resection, stereotactic radiation, targeted or immunotherapy.
Abstract: Peripheral pulmonary nodules are increasingly detected in patients screened for lung cancer or during disease progression of thoracic or extrathoracic malignancies. Sampling these lesions requires surgery, computed tomography (CT)-guided biopsy or bronchoscopic interventions. Bronchoscopic interventions are preferable because they have lower complications and often patients may not be ideal candidates for surgical or CT-guided biopsy. In addition, guidelines recommend diagnosis and staging in one single procedure. The diagnostic yield of existing advanced bronchoscopic techniques including electromagnetic navigation, radial probe ultrasonography, ultrathin bronchoscopy or virtual bronchoscopy remains suboptimal. The purpose of this paper is to codify the technique whereby a diagnostic bronchoscopy is performed using the new robotic platform. In the present report, I describe the technique for performing robotic-assisted bronchoscopy (RAB) using the Monarch™ platform (Auris Health, Inc., Redwood City, CA). Appropriate team training, patient selection, anesthesia settings, optimal tissue acquisition and processing, and prevention of complications are described and illustrated. RAB may be beneficial for patients with peripheral lung lesions that require biopsy prior to surgical resection, stereotactic radiation, targeted or immunotherapy.

Journal ArticleDOI
TL;DR: OVA-sensitized mice exhibit different pathophysiological patterns of asthma including expression of epithelial cell-derived cytokines depending on the OVA challenge route, suggesting that some heterogeneous phenotypes of human asthma can be replicated by varying the mode of delivery after OVA sensitization.
Abstract: The respiratory system is exposed to various allergens via inhaled and intranasal routes. Murine models of allergic lung disease have been developed to clarify the mechanisms underlying inflammatory responses and evaluate the efficacy of novel therapeutics. However, there have been no comparative studies on differences in allergic phenotypes following inhaled vs. intranasal allergen challenge. In this study, we compared the asthmatic features of mice challenged via different routes following allergen sensitization and investigated the underlying mechanisms. To establish ovalbumin (OVA)-induced allergic asthma models, BALB/c mice were sensitized to 20 μg OVA with 1 mg aluminum hydroxide by the intraperitoneal route and then challenged by inhalation or intranasal administration with 5% OVA for 3 consecutive days. Cellular changes and immunoglobulin (Ig) E levels in bronchoalveolar lavage fluid (BALF) and serum, respectively, were assessed. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining. Levels of T helper (Th)2 cytokines including interleukin (IL)-4, -5, and -13 in BALF and epithelial cytokines including IL-25 and -33 in BALF and lung tissues were measured by enzyme-linked immunosorbent assay and western blotting. Airway hyperresponsiveness (AHR) was evaluated by assessing airway resistance (Rrs) and elastance (E) via an invasive method. OVA-sensitized and challenged mice showed typical asthma features such as airway inflammation, elevated IgE level, and AHR regardless of the challenge route. However, H&E staining showed that inflammation of pulmonary vessels, alveolar ducts, and alveoli were enhanced by inhaled as compared to intranasal OVA challenge. PAS staining showed that intranasal OVA challenge induced severe mucus production accompanied by inflammation in bronchial regions. In addition, Th2 cytokine levels in BALF and AHR in lung were increased to a greater extent by inhalation than by intranasal administration of OVA. Epithelial cytokine expression, especially IL-25, was increased in the lungs of mice in the inhaled OVA challenge group. OVA-sensitized mice exhibit different pathophysiological patterns of asthma including expression of epithelial cell-derived cytokines depending on the OVA challenge route. Thus, some heterogeneous phenotypes of human asthma can be replicated by varying the mode of delivery after OVA sensitization.

Journal ArticleDOI
TL;DR: CTD-ILD, IPF, and unclassifiable ILD made up 80% of ILD diagnoses at ILD referral centers in Canada, while idiopathic NSIP was rare when adhering to recommended diagnostic criteria.
Abstract: The CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) is a multi-center, prospective registry designed to study the natural history of fibrotic interstitial lung disease (ILD) in adults. The aim of this cross-sectional sub-study was to describe the baseline characteristics, risk factors, and comorbidities of patients enrolled in CARE-PF to date. Patients completed study questionnaires and clinical measurements at enrollment and each follow-up visit. Environmental exposures were assessed by patient self-report and comorbidities by the Charlson Comorbidity Index (CCI). Baseline characteristics, exposures, and comorbidities were described for the overall study population and for incident cases, and were compared across ILD subtypes. The full cohort included 1285 patients with ILD (961 incident cases (74.8%)). Diagnoses included connective tissue disease-associated ILD (33.3%), idiopathic pulmonary fibrosis (IPF) (24.7%), unclassifiable ILD (22.3%), chronic hypersensitivity pneumonitis (HP) (7.5%), sarcoidosis (3.2%), non-IPF idiopathic interstitial pneumonias (3.0%, including idiopathic nonspecific interstitial pneumonia (NSIP) in 0.9%), and other ILDs (6.0%). Patient-reported exposures were most frequent amongst chronic HP, but common across all ILD subtypes. The CCI was ≤2 in 81% of patients, with a narrow distribution and range of values. CTD-ILD, IPF, and unclassifiable ILD made up 80% of ILD diagnoses at ILD referral centers in Canada, while idiopathic NSIP was rare when adhering to recommended diagnostic criteria. CCI had a very narrow distribution across our cohort suggesting it may be a poor discriminator in assessing the impact of comorbidities on patients with ILD.

Journal ArticleDOI
TL;DR: This work proposes a semi-automated method to quantify MLI that does not require specialized computer knowledge and uses a free, open-source image-processor and successfully applied this method to a murine model of particulate matter (PM) exposure.
Abstract: Quantifying morphologic changes is critical to our understanding of the pathophysiology of the lung. Mean linear intercept (MLI) measures are important in the assessment of clinically relevant pathology, such as emphysema. However, qualitative measures are prone to error and bias, while quantitative methods such as mean linear intercept (MLI) are manually time consuming. Furthermore, a fully automated, reliable method of assessment is nontrivial and resource-intensive. We propose a semi-automated method to quantify MLI that does not require specialized computer knowledge and uses a free, open-source image-processor (Fiji). We tested the method with a computer-generated, idealized dataset, derived an MLI usage guide, and successfully applied this method to a murine model of particulate matter (PM) exposure. Fields of randomly placed, uniform-radius circles were analyzed. Optimal numbers of chords to assess based on MLI were found via receiver-operator-characteristic (ROC)-area under the curve (AUC) analysis. Intraclass correlation coefficient (ICC) measured reliability. We demonstrate high accuracy (AUCROC > 0.8 for MLIactual > 63.83 pixels) and excellent reliability (ICC = 0.9998, p < 0.0001). We provide a guide to optimize the number of chords to sample based on MLI. Processing time was 0.03 s/image. We showed elevated MLI in PM-exposed mice compared to PBS-exposed controls. We have also provided the macros that were used and have made an ImageJ plugin available free for academic research use at https://med.nyu.edu/nolanlab. Our semi-automated method is reliable, equally fast as fully automated methods, and uses free, open-source software. Additionally, we quantified the optimal number of chords that should be measured per lung field.

Journal ArticleDOI
TL;DR: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis, from a multicentre study of 137 consecutive RA patients.
Abstract: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.

Journal ArticleDOI
TL;DR: This study provides compelling evidence that routine infection-prevention policies can greatly reduce nosocomial transmission of MERS and should be extended to all people treated by any medical employee who has contact with MERS patients.
Abstract: In 2015, South Korea experienced an outbreak of Middle East respiratory syndrome (MERS), and our hospital experienced a nosocomial MERS infection. We performed a comprehensive analysis to identify the MERS transmission route and the ability of our routine infection-prevention policy to control this outbreak. This is a case–cohort study of retrospectively analysed data from medical charts, closed-circuit television, personal interviews and a national database. We analysed data of people at risk of MERS transmission including 228 in the emergency department (ED) and 218 in general wards (GW). Data of personnel location and movement, personal protection equipment and hand hygiene was recorded. Transmission risk was determined as the extent of exposure to the index patient: 1) high risk: staying within 2 m; 2) intermediate risk: staying in the same room at same time; and 3) low risk: only staying in the same department without contact. The index patient was an old patient admitted to our hospital. 11 transmissions from the index patient were identified; 4 were infected in our hospital. Personnel in the ED exhibited higher rates of compliance with routine infection-prevention methods as observed objectively: 93% wore a surgical mask and 95.6% washed their hands. Only 1.8% of personnel were observed to wear a surgical mask in the GW. ED had a higher percentage of high-risk individuals compared with the GW (14.5% vs. 2.8%), but the attack rate was higher in the GW (16.7%; l/6) than in the ED (3%; 1/33). There were no transmissions in the intermediate- and low-risk groups in the ED. Otherwise 2 patients were infected in the GW among the low-risk group. MERS were transmitted to them indirectly by staff who cared for the index patient. Our study provide compelling evidence that routine infection-prevention policies can greatly reduce nosocomial transmission of MERS. Conventional isolation is established mainly from contact tracing of patients during a MERS outbreak. But it should be extended to all people treated by any medical employee who has contact with MERS patients. NCT02605109 , date of registration: 11th November 2015.

Journal ArticleDOI
TL;DR: The authors' simple-to-use nomogram model showed good discrimination and calibration in terms of predicting OSA, and had a C-index value of 0.839 according to the internal validation, which will help physicians better make decisions on PSG arrangement for patients referred to sleep center.
Abstract: The high cost and low availability of polysomnography (PSG) limits the timely diagnosis of OSA. Herein, we developed and validated a simple-to-use nomogram for predicting OSA. We collected and analyzed the cross-sectional data of 4162 participants with suspected OSA, seen at our sleep center between 2007 and 2016. Demographic, biochemical and anthropometric data, as well as sleep parameters were obtained. A least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data dimensionality, select factors, and construct the nomogram. The performance of the nomogram was assessed using calibration and discrimination. Internal validation was also performed. The LASSO regression analysis identified age, sex, body mass index, neck circumference, waist circumference, glucose, insulin, and apolipoprotein B as significant predictive factors of OSA. Our nomogram model showed good discrimination and calibration in terms of predicting OSA, and had a C-index value of 0.839 according to the internal validation. Discrimination and calibration in the validation group was also good (C-index = 0.820). The nomogram identified individuals at risk for OSA with an area under the curve (AUC) of 0.84 [95% confidence interval (CI), 0.83–0.86]. Our simple-to-use nomogram is not intended to replace standard PSG, but will help physicians better make decisions on PSG arrangement for the patients referred to sleep center.

Journal ArticleDOI
TL;DR: This study reports the largest UK survey exploring issues affecting patients with PH, and shows that despite the availability of new therapies, patients are still experiencing delays prior to diagnosis, and experiencing both emotional and financial impacts from the disease.
Abstract: Pulmonary Hypertension Association UK (PHA-UK) is the only charity in the UK especially for people affected by pulmonary hypertension (PH). To better understand the impact of PH on patients and carers beyond clinical symptoms, the PHA-UK carried out a cross-sectional survey on the effect of PH on daily living, along with a follow-up survey assessing the financial impact of PH. This is a descriptive cross-sectional survey of adult patients with PH in the UK. A quantitative survey of four key topics (time to diagnosis, quality of life [QoL], financial impact and specialist treatment), was made available to PHA-UK members and patients on PH therapy, with a follow-up financial impact survey sent to those responders who agreed to be contacted further. Data collection was carried out in January and February 2017 for the main survey, and November and December 2017 for the financial impact survey. The main survey was completed by 567 individuals, and the financial follow-up survey by 171. Mean age of responders was 69 ± 17 years with 70% female. 60% of respondents said PH had a major impact on their QoL, with 45% reporting that treatment and management improves their QoL ‘a lot’. The time between first experiencing symptoms and diagnosis was ≥1 year for 48% of patients, with 40% seeing 4+ doctors before diagnosis. 63% of patients reported financial worries. Patients in part-time and full-time work reported the greatest financial burden, with a 13 and 33% fall in monthly income respectively. Patients had positive experiences of treatment in specialist centres, with 62% rating their care ‘excellent’, and 92% saying they preferred travelling to a specialist centre rather than seeing a local non-specialist. This study reports the largest UK survey exploring issues affecting patients with PH. The study shows that despite the availability of new therapies, patients are still experiencing delays prior to diagnosis, and experiencing both emotional and financial impacts from the disease. By identifying the areas patients find most important in their treatment, this research can inform future care policies and long-term management to support patients living with PH and their families.

Journal ArticleDOI
TL;DR: Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS and showed improved symptom scores and a decreased number of exacerbations.
Abstract: Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice. To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma. From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations. The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14). Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.

Journal ArticleDOI
Wenping Zhang1, Jianchao Jia1, Zi Liu1, Dan Si1, Li-Jun Ma1, Guojun Zhang1 
TL;DR: MiR-223-3p could be utilized to predict sepsis secondary to pneumonia in patients with pneumonia and healthy controls through fluorescence real-time quantitative polymerase chain reaction (qRT-PCR).
Abstract: Sepsis biomarkers have limited specificity and sensitivity. Few studies have investigated microRNA (miRNA) biomarkers for sepsis secondary to pneumonia. This study aims to investigate the diagnostic and prognostic values of miRNAs in sepsis secondary to pneumonia. Sepsis 3.0 was used to diagnose sepsis. Screening was performed through the Agilent miRNA chip technology by using the following criteria: p 50 change. This study recruited 52 patients with pneumonia, including 31 males (59.6%) and 21 females (40.4%), 44 patients with sepsis secondary to pneumonia were diagnosed via Sepsis 3.0 (34 [77.3%] males and 10 [22.7%] females), and 21 healthy controls were used for miRNA verification. The miRNA levels were detected through fluorescence real-time quantitative polymerase chain reaction (qRT-PCR). Results: Fluorescence qRT-PCR detection showed that the miR-7110-5p and miR-223-3p expression levels in both patient groups were upregulated compared with those in the healthy controls. The expression levels differed between patients with pneumonia and those with sepsis secondary to pneumonia. The sensitivity and specificity of miR-7110-5p to differentiate sepsis from healthy controls were 84.2 and 90.5%, whereas those of miR-223-3p were 82.9 and 100%, respectively. Multivariate analysis of variance suggested that the presence of sepsis affected the miR-223-3p level (p = 0.041), whereas the presence of sepsis (p = 0.000) and the underlying disease (p = 0.025) influenced the miR-7110-5p level. MiR-223-3p could be utilized to predict sepsis secondary to pneumonia.

Journal ArticleDOI
Wanhong Yin1, Tongjuan Zou1, Yao Qin1, Jing Yang1, Yi Li1, Xueying Zeng1, Yan Kang1 
TL;DR: The lung ultrasound score is independently related to the 28-day mortality, as well as the APACHE II score and lactate level, in Intensive Care Unit shock patients.
Abstract: The lung ultrasound score has been regarded as a decent semiquantitative score to measure the lung aeration loss. The score has been proven to be valuable in diagnosing and monitoring lung pathology, but no studies have demonstrated its relationship to the outcome. We aimed to investigate the relationship between the lung ultrasound score and outcome in shock patients in the Intensive Care Unit. The data were extracted from the SHOCK-ICU study, a 14-month prospective study of shock patients in the Medical Intensive Care Unit in West China Hospital. A bivariate logistic regression model was established to identify the correlation between the lung ultrasound score on admission and the 28-day mortality. For subsequent analyses, we divided patients into lung ultrasound score quartiles, and survival analysis was performed using Cox stratified survival analysis and regression analysis with the Breslow method of ties. A total of 175 cases with a completed lung ultrasound exam were included. The mean APACHE II score was 23.7 ± 8.8, and the 28-day mortality was 46.3% (81/175). The multivariate analysis demonstrated that the lung ultrasound score was an independent risk factor for 28-day mortality, as well as the APACHE II score and lactate level. When divided into lung ultrasound score quartiles, after correcting for the APACHE II score, vasoactive use, PaO2/FiO2, and lactate level, the COX analysis reveals that a higher lung ultrasound score was related to a lower survival rate. Quartile 1 and quartile 2 had a significantly lower hazard ratio versus quartile 4 (OR 0.442[0.215–0.911]; 0.484[0.251–0.934], respectively). The lung ultrasound score is independently related to the 28-day mortality, as well as the APACHE II score and lactate level, in Intensive Care Unit shock patients. A higher elevated lung ultrasound score on admission is associated with a worse outcome. The study is registered on Clinical Trials. Trial registration: NCT03082326 ; retrospectively registered on 3 March 2017.

Journal ArticleDOI
TL;DR: Surfactant administration has not been shown to improve mortality and improve oxygenation for adult ARDS patients and Grading of Recommendations Assessment, Development, and Evaluation methodology indicated lack of firm evidence for a beneficial effect.
Abstract: Surfactant is usually deficiency in adult acute respiratory distress syndrome(ARDS) patients and surfactant administration may be a useful therapy. The aim of this study was to perform a meta-analysis of the effect of surfactant administration on outcomes of adult patients with acute respiratory distress syndrome. PubMed, EMBASE, Medline, Cochrane database, Elsevier, Web of Science and http://clinicaltrials.gov were searched and investigated until December 2017. Randomized controlled trials(RCTs) comparing surfactant administration with general therapy in adult patients with ARDS were enrolled. The primary outcome was mortality (7–10-day, 28–30-day and 90–180-day). Secondary outcome included oxygenation (PaO2/FiO2 ratio). Demographic variables, surfactant administration, and outcomes were retrieved. Sensitivity analyses were used to evaluate the impact of study quality issues on the overall effect. Funnel plot inspection, Egger’s and Begger’s test were applied to investigate the publication bias. Internal validity was assessed with the risk of bias tool. Random errors were evaluated with trial sequential analysis(TSA). Quality levels were assessed by Grading of Recommendations Assessment, Development, and Evaluation methodology(GRADE). Eleven RCTs with 3038 patients were identified. Surfactant administration could not improve mortality of adult patients [Risk ratio (RR) (95%CI)) = 1.02(0.93–1.12), p = 0.65]. Subgroup analysis revealed no difference of 7–10-day mortality [RR(95%CI)) = 0.89(0.54–1.49), p = 0.66], 28–30-day mortality[RR(95%CI) = 1.00(0.89–1.12), p = 0.98] and 90–180-day mortality [RR(95%CI) = 1.11(0.94–1.32), p = 0.22] between surfactant group and control group. The change of the PaO2/FiO2 ratio in adult ARDS patients had no difference [MD(95%CI) = 0.06(− 0.12–0.24), p = 0.5] after surfactant administration. Finally, TSA and GRADE indicated lack of firm evidence for a beneficial effect. Surfactant administration has not been shown to improve mortality and improve oxygenation for adult ARDS patients. Large rigorous randomized trials are needed to explore the effect of surfactant to adult ARDS patients.

Journal ArticleDOI
TL;DR: The main scientific goal is to identify the major pathogenic mechanisms associated with poor TB treatment outcomes, so that such pathways can be interrupted to avert long term TB sequelae.
Abstract: Up to fifty percent of microbiologically cured tuberculosis (TB) patients may be left with permanent, moderate or severe pulmonary function impairment. Very few studies have systematically examined pulmonary outcomes in patients to understand the pathophysiologic basis and long-term socio-economic consequences of this injury. The planned multi-country, multi-centre observational TB cohort study, aims to advance the understanding of the clinical, microbiological, immunological and socio-economic risk factors affecting long-term outcome of pulmonary TB. It will also determine the occurrence of reversible and irreversible socio-economic consequences to patients, their households and the health sector related to pulmonary TB disease and its treatment. We will enrol up to 1.600 patients with drug sensitive and multidrug-resistant pulmonary TB who are treated according to the local standard of care by the respective National TB Program. Recruitment is taking place at the time of TB diagnosis at four African study clinics located in The Gambia, Mozambique, South Africa and Tanzania. The primary outcome is the proportion of TB patients with severe lung impairment measured by spirometry at 24 months after TB treatment initiation. Biological samples, including sputum, urine and blood, for studying host- and pathogenic risk factors will be collected longitudinally and examined in a nested case-control fashion. A standardized quality of life questionnaire will be used together with a novel version of WHO’s generic patient cost instrument which has been adapted for the longitudinal study design. This study is an integral part of an overall strategy to fill a knowledge gap needed to improve TB treatment outcomes globally. The main scientific goal is to identify the major pathogenic mechanisms associated with poor TB treatment outcomes, so that such pathways can be interrupted to avert long term TB sequelae. National as well as supra-national stakeholders and decision makers have been integrated early in the study planning process to inform future treatment guidelines and national health policies. ClinicalTrials.gov: NCT03251196 , August 16, 2017.

Journal ArticleDOI
TL;DR: Male sex, older age, smoking, South Asian or First Nations ethnicity, and UIP pattern predicted decline in lung function and/or mortality in CTD-ILD.
Abstract: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is associated with reduced quality of life and poor prognosis. Prior studies have not identified a consistent combination of variables that accurately predict prognosis in CTD-ILD. The objective of this study was to identify baseline demographic and clinical characteristics that are associated with progression and mortality in CTD-ILD. Patients were retrospectively identified from an adult CTD-ILD clinic. The predictive significance of baseline variables on serial forced vital capacity (FVC), diffusion capacity (DLCO), and six-minute walk distance (6MWD) was assessed using linear mixed effects models, and Cox regression analysis was performed to assess impact on mortality. 359 patients were included in the study. Median follow-up time was 4.0 (IQR 1.5–7.6) years. On both unadjusted and multivariable analysis, male sex and South Asian ethnicity were associated with decline in FVC. Male sex, positive smoking history, and diagnosis of systemic sclerosis (SSc) vs. other CTD were associated with decline in DLCO. Male sex and usual interstitial pneumonia (UIP) pattern predicted decline in 6MWD. There were 85 (23.7%) deaths. Male sex, older age, First Nations ethnicity, and a diagnosis of systemic sclerosis vs. rheumatoid arthritis were predictors of mortality on unadjusted and multivariable analysis. Male sex, older age, smoking, South Asian or First Nations ethnicity, and UIP pattern predicted decline in lung function and/or mortality in CTD-ILD. Further longitudinal studies may add to current clinical prediction models for prognostication in CTD-ILD.

Journal ArticleDOI
Yang Xue1, Zhen Zhang1, Chu-Qiao Sheng1, Yumei Li1, Fei-Yong Jia1 
TL;DR: Diaphragm ultrasound has potential value in predicting the weaning outcome of critically ill children, and DTF and PImax presented better performance than other diaphragmatic parameters, however, DE has limited value in predicted weaning outcomes of children with MV.
Abstract: Multiple studies have shown that diaphragmatic ultrasound can better predict the outcome of weaning in adults. However, there are few studies focusing on children, leading to a lack of sufficient clinical evidence for the application of diaphragmatic ultrasound in children. The purpose of this study was to investigate the predictive value of diaphragm ultrasound for weaning outcomes in critically ill children. The study included 50 cases whose mechanical ventilation (MV) time was > 48 h, and all eligibles were divided into either the weaning success group (n = 39) or the weaning failure group (n = 11). Diaphragm thickness, diaphragmatic excursion (DE), and diaphragmatic thickening fraction (DTF) were measured in the zone of apposition. The maximum inspiratory pressure (PImax) was also recorded. The ventilatory treatment time (P = 0.002) and length of PICU stay (P = 0.013) in the weaning failure group was longer than the success group. Cut-off values of diaphragmatic measures associated with successful weaning were ≥ 21% for DTF with a sensitivity of 0.82 and a specificity of 0.81, whereas it was ≥0.86 cm H2O/kg for PImax with a sensitivity of 0.51 and a specificity of 0.82. The linear correlation analysis showed that DTF had a significant positive correlation with PImax in children (P = 0.003). Diaphragm ultrasound has potential value in predicting the weaning outcome of critically ill children. DTF and PImax presented better performance than other diaphragmatic parameters. However, DE has limited value in predicting weaning outcomes of children with MV. Current Controlled Trials ChiCTR1800020196, (Dec 2018).

Journal ArticleDOI
TL;DR: Lung cancer frequently developed in patients with IPF and was common in current-smoking men with rapid annual decline of 10% or more in forced vital capacity with rapid decline of FVC.
Abstract: Lung cancer is a common comorbidity of idiopathic pulmonary fibrosis (IPF) and has poor outcomes. The incidence and clinical factors related to development of lung cancer in idiopathic pulmonary fibrosis (IPF) are unclear. The aim of this study was to elucidate the cumulative incidence, risk factors, and clinical characteristics of lung cancer in IPF. In this retrospective study, we analyzed clinical data for 938 patients who were diagnosed with IPF without lung cancer between 1998 and 2013. Demographic, physiologic, radiographic, and histologic characteristics were reviewed. Cumulative incidence of lung cancer and survival were estimated by the Kaplan-Meier method. Risk factors of lung cancer development were determined by Cox proportional hazard analysis. Among 938 IPF patients without lung cancer at initial diagnosis, lung cancer developed in 135 (14.5%) during the follow-up period. The cumulative incidences of lung cancer were 1.1% at 1 year, 8.7% at 3, 15.9% at 5, and 31.1% at 10 years. Risk factors of lung cancer were male gender, current smoking at IPF diagnosis, and rapid annual decline of 10% or more in forced vital capacity (FVC). Patients who developed lung cancer were mostly elderly men with smoking history. Squamous cell carcinoma followed by adenocarcinoma was the most common histologic type. Lung cancer was frequently located in areas abutting or within fibrosis. Survival was significantly worse in patients with lung cancer compared to patients with IPF alone. Lung cancer frequently developed in patients with IPF and was common in current-smoking men with rapid decline of FVC.

Journal ArticleDOI
TL;DR: Frailty with mobility disability is common in COPD patients and severity of disease increases the risk, and it is possible that frail patients are more likely to quit smoking perhaps because of their disability and uncontolled disease.
Abstract: Frailty is a state of increased vulnerability that has a significant risk of unfavorable outcomes such as increased dependency and/or death, but little is known about frailty in people with chronic obstructive pulmonary disease (COPD). We aimed to determine the prevalence of frailty in COPD patients and to identify the associated risk factors. Two hundred fifty-seven COPD patients enrolled from primary care in Greece between 2015 and 2016. Physicians used structured interviews to collect cross-sectional data including demographics, medical history, symptoms and COPD Assessment Tool (CAT) or modified Medical Research Council Dyspnea scale (mMRC) score. Patients were classified into severity groups according to GOLD 2017 guidelines. Participants completed the The Frail Non-Disabled (FiND) questionnaire, exploring the frailty and disability domains. In the present analyses, frail patients with and without mobility disability were pooled and were compared to non-frail patients. Factors associated with frailty were analyzed using univariate and multivariate logistic regression. Mean (SD) age was 65 (12.3) with 79% males. The majority of patients suffered with frailty (82%) of which 76.8% had mobility disability. 84.2% were married/with partner and 55.4% retired. 55.6% were current smokers. Uncontrolled disease (≥10 CAT score) was reported in 91.1% and 37.2% of patients had ≥2 exacerbations in the past year. Dyspnea (38%) and cough (53.4%) were the main symptoms. Main comorbidities were hypertension (72.9%), hyperlipidaemia (24.6%) and diabetes (11%). Risk of frailty was significantly increased with age (OR; 95%CI: 1.05; 1.02–1.08), hypertension (2.25; 1.14–4.45), uncontrolled disease (≥10 CAT score 4.65; 1.86–11.63, ≥2 mMRC score 5.75 (2.79–11.85) or ≥ 2 exacerbations 1.73; 1.07–2.78), smoking cessation (ex compared to current smokers: 2.37; 1.10–5.28) and GOLD status (BD 1.86–11.63; mMRC-based: 5.75; 2.79–11.85). In multivariate regression smoking cessation and GOLD status remained significant. Gender, body mass index, occupational or marital status, symptoms and other comorbidities were not significant. Frailty with mobility disability is common in COPD patients and severity of disease increases the risk. It is possible that frail patients are more likely to quit smoking perhaps because of their disability and uncontolled disease. Routine assessment of frailty in addition to COPD control may allow early interventions for preventing or delaying progression of frailty and improvement in COPD disease.

Journal ArticleDOI
TL;DR: Medical thoracoscopy is generally a safe and effective method, not only in the diagnosis of undiagnosed pleural effusions, but also in the management of pleural diseases.
Abstract: Medical thoracoscopy is considered an overall safe procedure, whereas numbers of studies focus on complications of diagnostic thoracoscopy and talc poudrage pleurodesis. We conduct this study to evaluate the safety of medical thoracoscopy in the management of pleural diseases and to compare complications in different therapeutic thoracoscopic procedures. A retrospective study was performed in 1926 patients, 662 of whom underwent medical thoracoscopy for diagnosis and 1264 of whom for therapeutic interventions of pleural diseases. Data on complications were obtained from the patients, notes on computer system, laboratory and radiographic findings. Chi-square test was performed to compare categorical variables and Fisher’s exact test was used for small samples. The mean age was 51 ± 8.4 (range 21–86) years and 1117 (58%) were males. Diagnostic procedure was taken in 662 (34.4%) patients, whereas therapeutic procedure was taken in 1264 (65.6%) patients. Malignant histology was reported in 860 (44.6%) and 986 (51.2%) revealed benign pleural diseases. Eighty patients (4.2%) were not definitely diagnosed and they were considered as unidentified pleural effusion. One patient died during the creation of artificial pneumothorax, and the causes of death were supposed as air embolism or an inhibition of phrenic motoneurons and circulatory system. Complication of lung laceration was found in six patients (0.3%) and reexpansion pulmonary edema was observed in two patients (0.1%). Higher incidence of prolonged air leak was observed in bulla electrocoagulation group, in comparison with pleurodesis group. Moreover, pain and fever were the most frequently complications in pleurodesis group and cutaneous infection in entry site was the most frequently reported complication in pleural decortication of empyema group. Medical thoracoscopy is generally a safe and effective method, not only in the diagnosis of undiagnosed pleural effusions, but also in the management of pleural diseases. Mastering medical thoracoscopy well, improving patient management after the procedure and attempts to reduce the occurrence of post-procedural complications are the targets that physicians are supposed to achieve in the future.

Journal ArticleDOI
TL;DR: Almost all the genetic alterations studied showed a similar incidence in comparison with other Caucasian populations, and they probably have a scarce impact on the clinical management of Sardinians with lung adenocarcinoma.
Abstract: Lung cancer is one of the most incident neoplastic diseases, and a leading cause of death for cancer worldwide. Knowledge of the incidence of druggable genetic alterations, their correlation with clinical and pathological features of the disease, and their interplay in cases of co-occurrence is crucial for selecting the best therapeutic strategies of patients with non-small cell lung cancer. In this real-life study, we describe the molecular epidemiology of genetic alterations in five driver genes and their correlations with the demographic and clinical characteristics of Sardinian patients with lung adenocarcinoma. Data from 1440 consecutive Sardinian patients with a histologically proven diagnosis of lung adenocarcinoma from January 2011 through July 2016 were prospectively investigated. EGFR mutation analysis was performed for all of them, while KRAS and BRAF mutations were searched in 1047 cases; ALK alterations were determined with fluorescence in situ hybridization in 899 cases, and cMET amplifications in 788 cases. KRAS mutations were the most common genetic alterations involving 22.1% of the cases and being mutually exclusive with the EGFR mutations, which were found in 12.6% of them. BRAF mutations, ALK rearrangements, and cMET amplifications were detected in 3.2, 5.3, and 2.1% of the cases, respectively. Concomitant mutations were detected only in a few cases. Almost all the genetic alterations studied showed a similar incidence in comparison with other Caucasian populations. Concomitant mutations were rare, and they probably have a scarce impact on the clinical management of Sardinians with lung adenocarcinoma. The low incidence of concomitant cMET amplifications at diagnosis suggests that these alterations are acquired in subsequent phases of the disease, often during treatment with TKIs.