Severe Pulmonary Impairment Research Articles

Stereotactic ablative radiotherapy (SABR) for patients with lung tumor and severe pulmonary function impairment.

To evaluate clinical outcomes after SABR in a cohort of early-stage non-small cell lung cancer (NSCLC) or pulmonary metastases in chronic obstructive pulmonary disease (COPD) patients with forced expiratory volume in the first second predicted (FEV1) ≤ 50%. Retrospective single-center study was performed to analyze clinical outcomes and toxicities in COPD patients with severe lung dysfunction treated with SABR from 1st June 2015 to 31st October 2022. Thirty four patients (forty locations) were enrolled for analysis. Median follow-up was 2.9years. Median age was 73.5years (range, 65.6-80.1). FEV1 was 38% (range, 28.2-50.0) prior to radiotherapy. Median overall survival (OS) was 41.1months (95% CI 38.9-not reached). OS rates at 2-, 3-, and 5- years were 79%, 71%, and 36%, respectively. Cancer-specific survival rates at 2-, 3-, and 5- years were 96%, 96%, and 68%, respectively. Local control rates at 2-, 3-, and 5- years were 88%, 83%, and 83%, respectively. No grade 4 or 5 toxicity was observed. The most common acute toxicity was pneumonitis (38.2%), of which only 1 patient (2.9%) reported grade 3 acute toxicity. Lung SABR in patients with poor pulmonary function may be effective with acceptable toxicity.

What are the Barriers of Chronic Obstructive Pulmonary Disease (COPD) Patients in Smoking Cessation?

Smoking is the major determinant of developing chronic obstructive pulmonary disease (COPD). A substantial proportion of patients with COPD continue smoking although they have significant respiratory symptoms, exacerbation history and comorbidities. We aimed to find the associated factors and clinical features of the patients who maintain smoking. 200 current smokers and 132 former smokers with a spirometry-confirmed diagnosis of COPD were recruited from the outpatient department. Demographic characteristics, smoking backgrounds, treatment status, comorbidities, exacerbation history of the previous year, pulmonary function tests, blood biochemistry, dyspnea scales, symptom scores, and BECK anxiety scores were all recorded. No age and gender differences were found between current and former smokers. Compared to former smokers, current smokers were less qualified, had more cardiovascular diseases, more frequently exposed to tobacco smoke at home and at work place, more severe pulmonary function impairment, longer duration of COPD, longer time of smoking, earlier age of commencement in smoking, higher scores of BECK anxiety scores (BAI), higher levels of inflammatory markers in blood tests p<0.05. In multivariable analysis, lower values of FEV1%, higher scores of CAT and BAI, higher levels of platelet and CRP were found to decrease the likelihood of smoking cessation p<0.05. Additionally having diabetes, coronary artery disease and hypertension were inversely correlated with quitting smoking p<0.05. COPD is a systemic inflammatory disease. We found over half of the patients with COPD were currently smoking, despite the severity of their airflow limitation, symptoms and even the comorbidities. Furthermore, 2 out of 5 of the current smokers reported having moderate to severe anxiety. Dyspnea and inflammatory markers had negative effects on smoking cessation, and anxiety might be the cause that led these patients to keep smoking.

High-Resolution CT Scan Fibrotic Patterns in Stage IV Pulmonary Sarcoidosis: Impact on Pulmonary Function and Survival

Different patterns of fibrosis on high-resolution CT scans (HRCT) have been associated with reduced survival in some interstitial lung diseases. Nothing is known about HRCT scan patterns and survival in sarcoidosis. Will a detailed description of the extent and pattern of HRCT scan fibrosis in patients with stage IV pulmonary sarcoidosis impact pulmonary function and survival? Two hundred forty patients with stage IV sarcoidosis at two large tertiary institutions were studied. The earliest HRCT scan with fibrosis was reviewed for extent of fibrosis (< 10%, 10%-20%, and > 20%) and presence of bronchiectasis, upper lobe fibrocystic changes, basal subpleural honeycombing, ground-glass opacities (GGOs), large bullae, and mycetomas. Presence of sarcoidosis-associated pulmonary hypertension (SAPH) and pulmonary function testing performed within 1 year of HRCT were recorded. Patients were followed up until last clinic visit, death, or lung transplantation. The mean age was 58.4 years. Seventy-four percent were Black, 63%were female, and mean follow-up was 7.4 years. Death or LT occurred in 53 patients (22%). Thirty-one percent had > 20%fibrosis, 25%had 10%-20%fibrosis, and 44%had< 10%fibrosis. The most common HRCT abnormalities were bronchiectasis (76%), upper lobe fibrocystic changes (36%), and GGOs (28%). Twelve percent had basal subpleural honeycombing, and 32%had SAPH. Patients with > 20%fibrosis had more severe pulmonary impairment, were more likely to have SAPH (53%), and had worse survival (44%mortality; P< .001). Upper lobe fibrocystic changes, basal subpleural honeycombing, and large bullae were associated with worse pulmonary function and worse survival. Patients with basal subpleural honeycombing had the worst pulmonary function and survival (55%mortality; P< .001). GGOs were associated with worse pulmonary function but not worse survival, and mycetomas were associated with worse survival but not worse pulmonary function. A Cox proportional hazards model indicated that basal subpleural honeycombing (hazard ratio, 7.95), diffusion capacity for carbon monoxide< 40%(HR, 5.67) and White race (hazard ratio, 2.61) were independent predictors of reduced survival. HRCT scan features of fibrotic pulmonary sarcoidosis had an impact on pulmonary function and survival. Presence of >20%fibrosis and basal subpleural honeycombing are predictive of worse pulmonary function and worse survival in patients with stage IV pulmonary sarcoidosis.

Outpatient management of sarcoidosis in the COVID-19 pandemic

Introduction. COVID-19 infection alters the body’s immune tolerance, which can affect the course of systemic diseases caused by alterations in immune function. Patients with sarcoidosis, just like patients with systemic diseases, have impaired immune system function. They receive immunosuppressive therapy, so they are at risk of infectious diseases, including the viral ones.Aim. To investigate the course of sarcoidosis in the period 2020-2022, the incidence of COVID-19 infection in patients treated by the pulmonologist of the sarcoidosis-polyclinic office of the Krasnoyarsk Regional Clinical Hospital and to evaluate the incidence of sarcoidosis after COVID-19.Materials and methods. 301 outpatient charts of patients diagnosed with sarcoidosis were analyzed. Anamnestic data, information on vaccination against COVID-19, results of physical examination, multispiral computed tomography of thoracic organs in dynamics, data and methods of morphological verification, the volume of the received therapy for sarcoidosis were assessed.Results. There was evidence that the combination of active sarcoidosis and COVID-19 did not contribute to a severe course of viral infection and progression in the course of granulomatosis. In patients with baseline moderate or severe pulmonary function impairment due to sarcoidosis and long-term use of systemic glucocorticosteroids, no increase in the incidence of adverse COVID-19 outcomes was noted. When analyzing fatal cases, it became known that in the first case, chronic recurrent sarcoidosis and prolonged use of systemic glucocorticosteroids were the factors determining the adverse prognosis in COVID- 19 In the second case, the combination of sarcoidosis with cardiovascular disease, diabetes mellitus, and obesity were adverse outcome factors. New cases of sarcoidosis after COVID-19 have been reported, this may be explained by the interaction between SARS-CoV-2 and human immune system, imbalance of proand anti-inflammatory cytokines, disruption of interferon production. However, this statement requires further research.

Autophagy Modulators in Coronavirus Diseases: A Double Strike in Viral Burden and Inflammation.

Coronaviruses are the etiologic agents of several diseases. Coronaviruses of critical medical importance are characterized by highly inflammatory pathophysiology, involving severe pulmonary impairment and infection of multiple cell types within the body. Here, we discuss the interplay between coronaviruses and autophagy regarding virus life cycle, cell resistance, and inflammation, highlighting distinct mechanisms by which autophagy restrains inflammatory responses, especially those involved in coronavirus pathogenesis. We also address different autophagy modulators available and the rationale for drug repurposing as an attractive adjunctive therapy. We focused on pharmaceuticals being tested in clinical trials with distinct mechanisms but with autophagy as a common target. These autophagy modulators act in cell resistance to virus infection and immunomodulation, providing a double-strike to prevent or treat severe disease development and death from coronaviruses diseases.

COVID-19 in Lymphangioleiomyomatosis: An International Study of Outcomes and Impact of Mechanistic Target of Rapamycin Inhibition

Lymphangioleiomyomatosis is a rare low-grade neoplastic lung disease that occurs sporadically in women or in people with tuberous sclerosis complex. Mechanistic target of rapamycin (mTOR) inhibitors are used for patients with progressive or severe pulmonary impairment or extrapulmonary manifestations.1

Associations between severe pulmonary function and residual CT abnormalities in rehabilitating COVID-19 patients.

Coronavirus disease 2019 (COVID-19) spread around the world in 2020. Abnormal pulmonary function and residual CT abnormalities were observed in COVID-19 patients during recovery. Appropriate rehabilitation training is around the corner. The correlation between spirometric impairment and residual CT abnormality remains largely unknown. A cross-sectional study conducted on the pulmonary function of 101 convalescent COVID-19 patients before discharge. Multivariate analysis was used to establish a scoring system to evaluate the spirometric abnormality based on residual chest CT. Lung consolidation area >25% and severe-type COVID-19 were two independent risk factors for severe pulmonary dysfunction. Besides, a scoring system was established. People scoring more than 12 points have more chances (17 times) to get severe pulmonary function impairment before discharge. For the first time, a chest CT characteristics-based grading system was suggested to predict the pulmonary dysfunction of COVID-19 patients during convalescence in this study. This study may provide suggestions for pulmonary rehabilitation.

Inhibiting Connexin43/Zonula Occludens‐1 Interactions Improves Alcoholic Lung Barrier Function in vivo

Chronic alcohol consumption is well known to contribute to an array of health complications and increases the incidence and severity of acute respiratory distress syndrome (ARDS), an acute lung injury marked by severe pulmonary edema and impairment of normal gas exchange. Despite advancements in understanding its pathogenesis, the mortality rate for ARDS remains over 40% and there are currently no effective pharmacological treatments for ARDS. Chronic alcohol consumption contributes to the pathogenesis of ARDS by altering the tight junction composition of the pulmonary epithelium which is essential to maintain normal barrier function. In this study, we investigate the use of a pharmacological peptide, aCT1, which mimics the cytoplasmic carboxy-terminal PDZ binding motif of the gap junction protein Connexin43 (Cx43) to disrupt endogenous Cx43 from binding scaffold proteins, including the tight junction protein Zonula Occludens-1 (ZO-1). By inhibiting ZO-1 binding to Cx43, we hypothesize that more ZO-1 is available to associate with tight junction proteins, including claudins, to enhance epithelial barrier function. We have previously shown that chronic alcohol use exacerbates acute endotoxin-mediated lung injury by compromising both the alveolar and pulmonary capillary epithelial barriers. Here, we tested whether treatment with aCT1 strengthens alveolar barrier function and mitigates the effects of alcohol-mediated impairment of tight junctions. Male C57BL/6J mice were pair-fed 20% ethanol or water for 14 weeks to establish a chronic alcohol model in vivo. Mice were sedated and given an intratracheal instillation of 5mg/kg of the bacterial endotoxin lipopolysaccharide (LPS) derived from E. coli O55:B5 to induce a second, direct insult in the alcohol-primed lung to impact the lung epithelium. Mice were administered via nebulizer 1h post-LPS instillation either 5mg/kg of the aCT1 peptide or a scrambled control. Evans Blue (EB) dye was injected into mouse tail veins 24h after LPS instillation. To measure alveolar flooding, bronchoalveolar lavage fluid (BAL) was collected 1h later and EB in BAL was measured and normalized to serum EB. We found that administration of aCT1 decreased the leakage of EB dye from the blood into the alveolar air space in both water-fed and alcohol-fed mice, thus improving lung barrier function. This improvement in pulmonary leak suggests that aCT1 has the capacity to mitigate ARDS. Further investigation will determine whether aCT1 has a positive impact on short-term mortality rates due to endotoxemia and whether it can improve pulmonary barrier dysfunction due to other causes of acute lung injury.

Evidence-based of conjunctival COVID-19 positivity: An Italian experience: Gemelli Against COVID Group.

Background:The possible transmission of severe acute respiratory coronavirus 2 (SARS-CoV-2) by tears and conjunctiva is still debated.Methods:Main outcome was to investigate the agreement between nasopharyngeal swab (NPs) and conjunctival swabs (Cs) in patients with SARS-CoV-2 infection. We divided patients into four groups: (1) NPs and Cs both negative (C−NF−), (2) NPs positive and Cs negative (NFs+Cs−), (3) NPs negative and Cs positive (NFs−Cs+), and (4) NPs and Cs both positive (NFs−Cs+). The secondary outcomes were to correlate Cs results with systemic clinical parameters such as: oxygen saturation (SpO2), dyspnea degree (DP), radiologic pulmonary impairment based on chest radiography (XR) or computed tomography (CT), blood chemistry as D-Dimer (D-Dimer), fibrinogen, ferritin, lactate dehydrogenase (LDH), and C-reactive protein (C-RP).Results:A total of 100 conjunctival swabs in 50 patients with SARS-CoV-2 have been enrolled in this interventional clinical trials. Ocular signs (conjunctivitis) were present in five patients (10%). NPs and Cs highlighted a poor level of agreement (0.025; p = 0.404). Median SpO2 levels are the highest in the NF−C− group (98%) and the lowest (90%) in the group NF+C+ (p = 0.001). Pulmonary impairment was statistically significantly different between NFs and Cs groups (p = 0.019). Pulmonary impairment score increased from NFs−Cs− group (3.8 ± 3.9), to NFs+Cs+ group (6.7 ± 4.1). Intensive care unit patients showed higher COVID-19 Cs positivity in conjunctiva (12.5%) against hospitalized ones (5.8%).Conclusions:In patients hospitalized for SARS-CoV-2 the virus can be detected in conjunctival swab. Intensive care unit patients may reveal a higher COVID-19 presence in the conjunctiva. The most severe pulmonary impairment can be observed in NFs and Cs positivity.Trial registration:Clinicaltrials.gov registration.Ethical committee authorization:ID number: 0013008/20

Assessment of knowledge, attitude, and practice towards pulmonary rehabilitation among COPD patients: A multicenter and cross-sectional survey in China

BackgroundPulmonary rehabilitation (PR) has been recognized to be an evidence-based treatment recommended for chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate COPD patients’ knowledge, attitudes and practices towards PR in China. Methods1138 COPD patients from 13 hospitals were enrolled in this cross-sectional study. A questionnaire designed based on an official statement was completed by the participants. Effects of PR in patients were investigated. ResultsMean score of the knowledge portion was only 7.76, while 46.22% of the participants believed they needed PR. Attendance rate was 24.69%. Financial conditions and hospitalization were contributing factors for scores, attendance rate, and belief in demands for PR therapy. Severe pulmonary function impairment indicated more demands for PR (OR = 0.18) and higher uptake rate (OR = 0.30). There was a weak correlation between smoking status (rho = −0.060), diagnosis year (rho = 0.094), frequency of exacerbations (rho = 0.059) and grades. High CAT score is a facilitator for attitudes towards PR (OR = 0.022). 93.24% of patients claimed that their exercise tolerance improved with PR therapy. The improvements were positively associated with needs (rho = 0.20), family support (rho = 0.22), grades (rho = 0.18), and monthly income of the family (rho = 0.14), but negatively correlated with age (rho = −0.16), exacerbations (rho = −0.15), and CAT score (rho = −0.13). ConclusionsThis study suggested poor perception, disbelief in the need for PR, and limited uptake of PR among COPD patients in China, and revealed the significant factors involved. The findings of this study may assist health professionals in developing targeted strategies to promote PR and improve access and uptake of PR.

Effectiveness and safety of a modified (rib ends fixed under transverse process) thoracoplasty for rib hump deformity in adults with severe thoracic scoliosis: A retrospective study.

Razor back deformity is one of the most noticeable problems of severe scoliosis. Thoracoplasty has been reported to be a useful approach to correct the rib hump deformity. However, the outcomes of thoracoplasty in patients with severe, rigid, thoracic scoliosis have not yet been evaluated.To evaluate the effectiveness and safety of a modified technique of thoracoplasty (rib ends fixed under transverse process) for rib hump deformity in adults with severe thoracic scoliosis and severe pulmonary dysfunction.Patients with severe thoracic scoliosis and severe pulmonary dysfunction who underwent staged surgical strategy including halo-pelvic traction, spinal osteotomy combined with the modified thoracoplasty were included. To avoid paradoxical breathing result from multiple rib resections and enlarge the capacity of thoracis, the ends after rib resection were fixed under transverse process compared with conventional thoracoplasty. Patients were excluded on the basis of pulmonary diseases and inadequate follow-up. Data on deformity correction and pulmonary complications were reviewed. A t test was performed on the pre- and postoperative data of pulmonary function, height of the rib hump deformity, and total lung area.Eighteen patients (5 men and 13 women) with a major thoracic curve of >130° were included. The mean age of patients was 25.3 ± 3.6 years (range, 19–32 years), with an average length of follow-up of 30.2 months. After application of halo-pelvic traction, the mean major thoracic curve decreased from 168.2° ± 14.28° to 97.3° ± 10.75° and the thoracic kyphosis decreased from 159.4° ± 20.60° to 94.8° ± 9.58°. On average, 6.3 (range, 4–8) ribs were resected. The height of the rib hump decreased from 84.6 ± 13.3 to 15.3 ± 3.4 mm. The average predicted forced vital capacity (FVC%) before surgery was 37.2 ± 13.30%, indicative of severe pulmonary impairment, with a small but non-significant improvement in the FVC% at the final follow-up. The mean total lung area increased from 2583.2 ± 501.36 to 2890.1 ± 537.30 mL at the last follow-up. No severe pulmonary complications occurred.Our modified approach to thoracoplasty procedure is effective and safe in correcting a razor back deformity in patients with severe, rigid, scoliosis, and severe pulmonary dysfunction, without causing any significant change in long-term pulmonary function.

Observational study on off-label use of tocilizumab in patients with severe COVID-19

BackgroundIn December 2019 a novel coronavirus designated SARS-CoV-2 was identified, and the disease COVID-19 has caused many deaths. SARS-CoV-2 infection has been associated with the development of cytokine storm (including...

Characteristics of pulmonary function in infants and young children with pertussis-like coughing

To study the characteristics of pulmonary function in children with pertussis-like coughing caused by different pathogen infections. The data on etiology and tidal breathing pulmonary function were collected from 95 hospitalized infants and young children with pertussis-like coughing. The tidal breathing pulmonary function was compared between these children and 67 healthy children. According to the type of pathogen, the children with pertussis-like coughing were classified to 6 groups: pertussis (n=17), viral infection (n=23), tuberculosis infection (n=6), Mycoplasma infection (n=9), other bacterial infection (n=8), and unknown pathogen (n=32). Among the 95 children with pertussis-like coughing, 15 (16%) had mild obstructive ventilatory dysfunction, 30 (32%) had moderate obstructive ventilatory dysfunction, and 22 (23%) had severe obstructive ventilatory dysfunction. Compared with the normal control group, the children with pertussis-like coughing had significant reductions in inspiratory-to-expiratory time ratio, ratio of time to peak tidal expiratory flow to total expiratory time (tPF%tE), and ratio of volume to peak tidal expiratory flow to total expiratory volume (vPF%vE) (P<0.05). The tuberculosis infection and Mycoplasma infection groups had a significantly lower tidal volume than the normal control group (P<0.05). All pathogen infection groups except the tuberculosis infection group had significantly lower tPF%tE and vPF%vE than the normal control group (P<0.05). The pertussis group had significantly lower tPF%tE and vPF%vE than the other infection groups (P<0.05). Most of children with pertussis-like coughing have abnormal pulmonary functions. The children with Bordetella pertussis infection have the most severe pulmonary function impairment. Tidal breathing pulmonary function test may provide a reference for pathogen analysis of children with pertussis-like coughing.

Feasibility and accuracy of SPECT myocardial perfusion imaging in end-stage lung disease

BackgroundCoronary artery disease (CAD) is associated with increased mortality in patients with chronic lung disease. However, non-invasive diagnostic of CAD is difficult, especially in patients with more advanced disease. Therefore, we aimed to assess the feasibility and accuracy of SPECT-myocardial perfusion imaging (MPI) stress testing with regadenoson in patients with end-stage lung disease (ELD) undergoing assessment of stable CAD. MethodsBetween January 2012 and May 2018, 102 patients with ELD, who were referred to our institution for lung transplant evaluation, were assessed retrospectively. All patients underwent both stress SPECT-MPI as well as coronary angiography. ResultsThe mean age in our population was 57±6 years. All patients had severe pulmonary function impairment. During stress SPECT-MPI 14 patients (14%) reported regadenoson-related symptoms, but only 2 patients (2%) required medical treatment. Coronary angiography revealed obstructive CAD in 20 patients (20%). Among those, 5 patients had abnormal SPECT-MPI and PCI was performed in 3 patients accordingly. In 14 patients with obstructive CAD, revascularization was deferred based on normal SPECT-MPI findings. ConclusionsSPECT-MPI using regadenoson is well tolerated in patients with ELD and can help to make decisions about coronary revascularization before lung transplant.

Adult outcomes of childhood bronchiectasis

ABSTRACT Recent literature has highlighted the importance of transition from paediatric to adult care for children with chronic conditions. Non-cystic fibrosis bronchiectasis is an important cause of respiratory morbidity in low-income countries and in indigenous children from affluent countries; however, there is little information about adult outcomes of childhood bronchiectasis. We reviewed the clinical course of 31 Alaska Native adults 20–40 years of age from Alaska’s Yukon Kuskokwim Delta with childhood bronchiectasis. In patients with chronic suppurative lung disease, a diagnosis of bronchiectasis was made at a median age of 4.5 years by computerised tomography (68%), bronchogram (26%), and radiographs (6%). The patients had a median of 75 lifetime respiratory ambulatory visits and 4.5 hospitalisations. As children, 6 (19%) experienced developmental delay; as adults 9 (29%) experienced mental illness or handicap. Four (13%) patients were deceased, four (13%) had severe pulmonary impairment in adulthood, 17 (54%) had persistent or intermittent respiratory symptoms, and seven (23%) were asymptomatic. In adulthood, only five were seen by adult pulmonologists and most had no documentation of a bronchiectasis diagnosis. Lack of provider continuity, remote location and co-morbidities can contribute to increased adult morbidity. Improving the transition to adult care starting in adolescence and educating adult providers may improve care of adults with childhood bronchiectasis.

Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation.

Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence of lower respiratory tract infection, and hypoxemia. We described IPS incidence and mortality within 120 and 365 days after HCT. We examined conditioning intensity (nonmyeloablative versus myeloablative with high-dose total body irradiation [TBI] versus myeloablative with low-dose TBI) as an IPS risk factor in a time-to-event analysis using Cox models, controlled for age at transplant, HLA matching, stem cell source, and pretransplant Lung function Score (a combined measure of impairment in Forced Expiratory Volume in the first second (FEV1) and Diffusion capacity for carbon monoxide (DLCO)). Among 1829 HCT recipients, 67 fulfilled IPS criteria within 120 days (3.7%). Individuals who developed IPS were more likely to be black/non-Hispanic versus other racial groups and have severe pulmonary impairment but were otherwise similar to participants without IPS. In adjusted models, myeloablative conditioning with high-dose TBI was associated with increased risk of IPS (hazard ratio, 2.5; 95% confidence interval, 1.2 to 5.2). Thirty-one patients (46.3%) with IPS died within the first 120 days of HCT and 47 patients (70.1%) died within 365 days of HCT. In contrast, among the 1762 patients who did not acquire IPS in the first 120 days, 204 (11.6%) died within 120 days of HCT and 510 (29.9%) died within 365 days of HCT. Our findings suggest that although the incidence of IPS may be declining, it remains associated with post-transplant mortality. Future study should focus on early detection and identifying pathologic mediators of IPS to facilitate timely, targeted therapies for those most susceptible to lung injury post-HCT.

TB sequel: incidence, pathogenesis and risk factors of long-term medical and social sequelae of pulmonary TB \u2013 a study protocol

BackgroundUp 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.MethodsWe 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.DiscussionThis 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.Trial registrationClinicalTrials.gov: NCT03251196, August 16, 2017.

Genetic analyses in a cohort of 191 pulmonary arterial hypertension patients

BackgroundPulmonary arterial hypertension (PAH) is a progressive and fatal disorder associated with high pulmonary artery pressure. Genetic testing enables early diagnosis and offers an opportunity for family screening. To identify genetic mutations and help make a precise diagnosis, we performed genetic testing in 191 probands with PAH and tried to analyze the genotype-phenotype correlation.MethodsInitially, PAH samples (n = 119) were submitted to BMPR2 screening using Sanger sequencing. Later, we developed a PAH panel test to identify causal mutations in 13 genes related to PAH and tried to call BMPR2 copy number variations (CNVs) with the panel data. Multiplex ligation-dependent probe amplification (MLPA) was used to search for CNVs in BMPR2, ACVRL1 and ENG. Notably, EIF2AK4 gene was also involved in the panel, which allowed to distinguish pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH) patients from idiopathic PAH (IPAH). Characteristics of patients were compared using t test for continuous variables.ResultsPathogenic BMPR2 mutations were detected most frequently in 32 (17.9%) IPAH and 5 (41.7%) heritable PAH (HPAH) patients by sequencing, and 12 BMPR2 CNVs called from the panel data were all successfully confirmed by MLPA analysis. In addition, homozygous or compound heterozygous EIF2AK4 mutations were identified in 6 patients, who should be corrected to a diagnosis of PVOD/PCH. Genotype-phenotype correlation analysis revealed that PAH patients with BMPR2 mutations were younger at diagnosis (27.2y vs. 31.6y, p = 0.0003) and exhibited more severe pulmonary hemodynamic impairment and a worse cardiac index compared with those without BMPR2 mutations.ConclusionsThe panel assay represented a highly valuable tool in PAH genetic testing, not only for the detection of small sequence alterations, but also for an indication of BMPR2 CNVs, which had implications for the specific samples to perform further MLPA assay. Analyses of PAH causal genes have a great help to clinical diagnosis and deep implications in disease treatment.

Unilateral Upper Lung Field Pulmonary Fibrosis Radiologically Consistent with Pleuroparenchymal Fibroelastosis after Thoracotomy: A New Disease Entity Related to Thoracotomy

Background: Pleuroparenchymal fibroelastosis (PPFE) is a rare bilateral idiopathic interstitial pneumonia defined by pleural-parenchymal involvement. In clinical practice, we encountered patients with upper lung field pulmonary fibrosis (Upper-PF), which was radiologically consistent with PPFE, but apparently limited to the unilateral lung. Objectives: The purpose of the study was to clarify the clinical characteristics in those patients. Methods: We examined the medical records of all the consecutive patients from 2012 to 2016 to see whether there were patients having unilateral Upper-PF. Results: We found 6 patients with unilateral Upper-PF. The most common symptom was dyspnea, and all patients had a low body mass index and severe restrictive pulmonary impairment. Notably, all patients had a history of thoracotomy for resecting lung or esophageal cancer, and the lesions were limited to the operated side. Dynamic breathing chest MRI showed an impaired thoracic movement in the operated side. Serial chest CT from prethoracotomy to the first visit was obtained in 5 patients: before thoracotomy, only a slight apical cap, defined as a wedge- and triangle-shaped opacity with broad pleural contact, was observed only in the operated side, but progressed into the lesion after a median of 8.4 years following thoracotomy. After the first visit, the unilateral lesion rapidly deteriorated in all patients. Conclusions: Unilateral Upper-PF had some characteristics in common with PPFE. Because the lesion was limited to the operated side, unilateral Upper-PF would be a new disease entity related to thoracotomy. Our results indicate that thoracotomy impairs thoracic movement in the operated side and subsequently triggers unilateral Upper-PF development, especially in patients with an apical cap.

Sex-related differences in bronchial parameters and pulmonary function test results in patients with chronic obstructive pulmonary disease based on three-dimensional quantitative computed tomography.

ObjectiveThis study was performed to evaluate the effect of sex on bronchial parameters and the predicted forced expiratory volume in 1 s expressed as a percentage of the forced vital capacity (FEV1% pred) on pulmonary function testing.MethodsThe data of 359 patients with chronic obstructive pulmonary disease (COPD) with available FEV1% pred and computed tomography (CT) images were retrospectively reviewed. FACT-Digital lung TM software (DeXin, Xi’an, China) was used to perform fully automated three-dimensional CT quantitative measurements of the bronchi. Generation 5 to 7 bronchi were measured, and the parameters analyzed were the lumen diameter (LD), wall thickness (WT), lumen area (LA), and WA% [WA / (WA + LA) × 100%].ResultsIn the smoking, smoking cessation, and nonsmoking groups, women had a significantly larger WA% and smaller LD, WT, and LA than men. The FEV1% pred was significantly lower in women than men in the smoking and smoking cessation groups. The FEV1% pred was significantly higher in women than men in the nonsmoking group.ConclusionSex-related differences may partially explain why smoking women experience more severe pulmonary function impairment than men among patients with COPD.