A case of nonmucinous pulmonary micropapillary adenocarcinoma mimicking pulmonary tuberculosis

We report a rare case of nonmucinous pulmonary micropapillary adenocarcinoma mimicking pulmonary tuberculosis. A 68-year-old woman was hospitalized with hemoptysis. Her computed tomography revealed cavities and tree-in-bud appearance similar to the extensive form of pulmonary tuberculosis. However, histopathological findings of transbronchial biopsies of all lesions revealed adenocarcinoma and no pulmonary tuberculosis. Tree-in-bud appearance may relate to the floating micropapillary tufts in alveolar spaces. If pulmonary carcinoma is complicated by pulmonary tuberculosis, patients must be isolated and disadvantaged in cancer treatments. Therefore, recognizing this case may be therapeutically useful for respiratory physicians treating both diseases.     

A case of exogenous lipoid pneumonia diagnosed by transbronchial lung cryobiopsy

A 57-year-old man visited a referral physician due to abnormal chest shadows. Transbronchial lung biopsy (TBLB) failed to diagnose his condition. As antibiotics and systemic steroids did not improve the condition, he was referred to our hospital. A second TBLB in our hospital also failed to diagnose the disease. Transbronchial lung cryobiopsy (TBLC) was performed using radial endobronchial ultrasound with guide sheath (EBUS-GS), and the patient was diagnosed with lipoid pneumonia. Right upper lobe resection was performed, and lipoid pneumonia was confirmed from the surgical specimen. We report a case of lipoid pneumonia diagnosed by EBUS-GS TBLC.     

Disappearance of recurrent thymic epithelial tumor following corticosteroid and cyclosporine treatment: A case report

Thymic epithelial tumors (TETs) are considered orphan neoplasms, and treatment options for recurrent or metastatic stages are limited. Here, we have reported a case of recurrent TET that showed complete remission after receiving high-dose corticosteroids followed by low-dose corticosteroids and cyclosporine. No recurrence was observed for the next 2 years. The effects of corticosteroids on the TET and the associated pure red cell aplasia led to adjustment of the diagnosis from thymic carcinoma to thymoma. Low-dose corticosteroids and cyclosporine might be the reason for remission maintenance.     

Treatment efficacy of LAMA versus placebo for stable chronic obstructive pulmonary disease: A systematic review and meta-analysis

BackgroundFour long-acting muscarinic antagonists (LAMAs), tiotropium, glycopyrronium, aclidinium, and umeclidinium, are currently available for the treatment of stable chronic obstructive pulmonary disease (COPD). However, no integrated analysis has sought to determine the effectiveness of these LAMAs. Thus, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LAMA versus placebo in patients with stable COPD.MethodsA literature search of relevant randomized control trials that administered LAMA to stable COPD patients was conducted, and the exacerbations, quality of life (QoL), dyspnea score, lung function, and adverse event of patients were evaluated.ResultsA total of 33 studies were included in this meta-analysis. LAMA significantly decreased the frequency of exacerbations compared to the placebo (OR 0.75; 95% CI 0.66 to 0.85; P < 0.001). The mean changes in the St George's Respiratory Questionnaire score (mean difference, ?3.61; 95% CI, ?4.27 to ?2.95; P < 0.00001), transitional dyspnea index score (mean difference 1.00; 95% CI 0.83 to 1.17; P < 0.00001), and trough FEV₁ (mean difference 0.12; 95% CI 0.11 to 0.13; P < 0.0001) indicated significantly greater improvement in the LAMA group than the placebo group. The number of withdrawals due to adverse events in the LAMA group was significantly fewer than that in the placebo group (OR -0.02; 95% CI -0.03 to ?0.01; P = 0.002).ConclusionLAMA is superior to placebo due to lower frequency of exacerbations and adverse events, as well as higher trough FEV₁, QoL, and dyspnea score for stable COPD.     

Lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for Mycobacterium avium complex pulmonary disease

BackgroundEthambutol ocular toxicity is a major problem during combination chemotherapy for Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD) due to years-long therapy for MAC.ObjectivesThis study aimed to identify the lower dose of daily ethambutol that can reduce ocular toxicity.MethodsWe retrospectively reviewed the medical records of 312 patients who visited The University of Tokyo Hospital between January 2007 and December 2017 for nontuberculous mycobacterial pulmonary disease. Seventy-six patients with MAC-PD who were treated with combination chemotherapy for the first time were analyzed in this study.ResultsEthambutol was discontinued because of visual symptoms in 13 patients (17%), 7 of whom were diagnosed with ethambutol ocular neuropathy. The dose per body weight was significantly higher in patients who developed ocular neuropathy than in those who did not (15.4 mg/kg/d vs. 12.5 mg/kg/d, respectively; p = 0.048). We assigned patients to higher or lower dose groups according to the median dose of 12.5 mg/kg/d. Although ocular neuropathy developed in 6 out of 38 patients in the higher dose group, ocular neuropathy developed in 1 out of 38 patients in the lower dose group (16% vs. 3%, respectively; p = 0.038). The failures of sputum culture conversion and radiological improvement were not significantly different between the two groups (p = 0.638 and 0.305, respectively). Macrolide resistance developed in one patient per group during follow-up (3% per group, p = 0.945).ConclusionsA lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for pulmonary MAC infection.     

Lobar distribution of non-emphysematous gas trapping and lung hyperinflation in chronic obstructive pulmonary disease

BackgroundLung hyperinflation in chronic obstructive pulmonary disease (COPD) is closely associated with emphysema and non-emphysematous gas trapping, termed functional small airway disease (fSAD), on inspiratory and expiratory computed tomography (CT). Because the cranial-caudal emphysema distribution affects pulmonary function and fSAD may precede emphysema on CT, we tested the hypothesis that lobar fSAD distribution would affect lung hyperinflation differently in COPD with minimal and established emphysema.MethodsThe volume percentages of fSAD and emphysema (fSAD% and Emph%) over the upper and lower lobes were measured using inspiratory and expiratory CT in 70 subjects with COPD. Subjects were divided into those with minimal and established emphysema (n = 36 and 34) using a threshold of 10% Emph% in the whole lung.ResultsIn the minimal emphysema group, fSAD% in the upper and lower lobes was positively correlated with functional residual capacity (FRC) and residual volume to total lung capacity ratio (RV/TLC), and the correlation of fSAD% with RV/TLC was greater in the lower lobes. Conversely, in the established emphysema group, fSAD% in the upper and lower lobes was correlated with RV/TLC, but not with FRC. In multivariate analysis, fSAD% in the lower lobes, but not in the upper lobes, was associated with RV/TLC in subjects with minimal emphysema after adjusting for age, smoking status, and bronchodilator use.ConclusionNon-emphysematous gas trapping in the upper and lower lobes has a distinct physiological effect, especially in COPD with minimal emphysema. This local evaluation might allow sensitive detection of changes in lung hyperinflation in COPD.     

The role of viral infections in pulmonary exacerbations of patients with non-cystic fibrosis bronchiectasis: A systematic review

BackgroundBronchiectasis is a cause of increased morbidity of the respiratory system. Exacerbations among patients with non-CF (cystic fibrosis) bronchiectasis result in reduced pulmonary function and poor quality of life. While the role of bacteria in triggering exacerbations in patients with non- CF bronchiectasis has been well studied, little is known about viral infections in these patients. We aimed to review the evidence on the role of respiratory viruses in the exacerbations of non-CF bronchiectasis.MethodsRelevant literature was searched on the MEDLINE/PubMed database. Seven studies satisfied the criteria and were included in this review.ResultsAccording to the included articles, respiratory viruses are often identified in exacerbations of patients with non-CF bronchiectasis with the most frequent being human rhinovirus and influenza viruses. When a virus is isolated during an exacerbation patients have more symptoms from the upper respiratory tract. One study showed that detection of Epstein- Barr virus among patients with non-CF bronchiectasis is correlated with faster reduction of pulmonary function and progression of the disease.ConclusionViruses seem to have a role in the exacerbation of patients with non-CF bronchiectasis. However, the exact nature and importance of this role remain elusive. Viruses are also isolated during the stable period of the disease. Further well-designed studies are necessary to clarify this complex issue.     

Prevalence of pulmonary embolism in patients with obstructive sleep apnea and chronic obstructive pulmonary disease: The overlap syndrome

ObjectiveGrowing evidence indicates that both obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) may be closely associated with the prevalence of pulmonary embolism (PE). However, the relationship of overlap syndrome (OS) (coexistence of OSA and COPD) with PE is unclear. The purpose of this study was to investigate whether OS were associated with increased PE prevalence.MethodsWe performed a retrospective chart review of patients who underwent sleep study at Beijing An Zhen Hospital from 2011 to 2014. The association of OS with PE prevalence was estimated by using logistic regression models.ResultsIn contrast to control patients (neither OSA nor COPD), those subjects with OS had higher odds of PE (OR9.61; 95%CI 4.02–21.31, p < 0.001) with significance persisting after adjusting for covariates (OR 5.66; 95%CI 1.80–16.18, p = 0.004). Meanwhile, patients with OS compared with those with isolated OSA also had significantly higher odds of PE in univariate (OR 4.79; 95%CI 2.04–10.33, p = 0.0007) and adjusted models (OR 3.89; 95%CI 1.27–10.68, p = 0.019). In subgroup analysis, patients with OS had higher odds of PE than control group among male subjects (OR 8.12, 95%CI1.86–31.87, p = 0.007) and patients ≥ 58years (OR 5.50, 95%CI 1.51–18.14, p = 0.012) in multivariable models. Percentage of total sleep time with saturation lower than 90% (T90) ≥ 2.6% was significantly associated with prevalence of PE (OR 4.72, 95%CI1.34–19.83, p = 0.015) in subgroup of patients older than 58.ConclusionsOS is independently associated with PE prevalence. Longitudinal studies are needed to better understand the relationship with incident PE.     

Bronchoscopy for the diagnosis of nontuberculous mycobacterial pulmonary disease: Specificity and diagnostic yield in a retrospective cohort study

BackgroundBronchoscopy is a recognized method for obtaining specimens for the diagnosis of nontuberculous mycobacterial pulmonary disease (NTM-PD). However, its diagnostic properties remain to be elucidated. The aim of this study was to determine the specificity of bronchoscopy for the diagnosis of NTM-PD, and to examine the diagnostic yield of bronchoscopy for detecting nontuberculous mycobacteria (NTM) when patients cannot expectorate sputum with NTM.MethodsThis retrospective cohort study included 2657 patients who underwent bronchoscopy and mycobacterial culture between January 2004 and June 2018 in a tertiary care center in Tokyo, Japan. To examine the specificity of bronchoscopy, the first cohort comprised patients who underwent bronchoscopy for the diagnosis of lung cancer and mycobacterial culture. To investigate the diagnostic yield, patients with nodular bronchiectasis who underwent bronchoscopy for the diagnosis of NTM-PD were enrolled into the second cohort.ResultsIn total, 919 patients were diagnosed with lung cancer, 19 patients showed positive culture for NTM, and 14 patients showed findings for NTM-PD. Accordingly, the specificity was calculated as 900/905 (99.4%). In addition, NTM-PD was suspected before bronchoscopy in 199 patients; the diagnostic yield was 105/199 (52.8%). Four factors were associated with NTM-PD: upper lobe examination, absence of specific bacteria, absence of connective tissue disease, and a higher total computed tomography score.ConclusionsBronchoscopy has a high specificity for the diagnosis of NTM-PD. In addition, even when NTM is undetected in sputum, bronchoscopy may detect mycobacteria in approximately half of the patients suspected of having NTM-PD.     

Recurrence of idiopathic pulmonary hemosiderosis in adults with childhood onset: A case report and literature review

We describe a rare case of a 20-year-old Japanese man with idiopathic pulmonary hemosiderosis (IPH) recurrence in adults with childhood onset (racIPH). IPH commonly occurs in children, and data regarding racIPH are lacking. A review of the literature showed that only five cases of racIPH have been reported (including the present case) and that racIPH shows features that are intermediate between childhood- and adult-onset IPH with respect to age and a lower frequency of smoking history. We also found that the degree of anemia was usually not severe, and a favorable response to corticosteroid therapy is expected in racIPH.     

A modified GAP model for East-Asian populations with idiopathic pulmonary fibrosis

BackgroundThe easy-to-calculate gender, age, and lung physiology (GAP) model shows good predictive and discriminative performance in the prognosis of idiopathic pulmonary fibrosis (IPF). However, the GAP model was not effective in predicting the prognosis accurately in previous Japanese and Korean IPF cohort studies. Therefore, we developed a modified GAP model for the East-Asian populations by weighing the GAP variables. The validity of the modified GAP model was subsequently evaluated in East-Asian IPF patients.MethodsThe derivation cohort comprised 326 patients with IPF. Weights of the variables were adjusted on the basis of coefficients derived from Cox regression models. The total points were distributed to the three stages of the disease so that the number of patients included in each stage was appropriate. The validity of the modified model was analyzed in another Japanese cohort of 117 patients with IPF and a nationwide cohort of Korean patients with IPF.ResultsPredicted survival rates differed significantly in the derivation cohort using the modified GAP model for each stage of IPF (log-rank test: stage I vs. stage II, p < 0.001; stage II vs. stage III, p < 0.001). Model performance improved according to Harrell's C-index (at three years: 0.696 in the original GAP model to 0.738 in the modified model). The performance of the modified model was validated in the Japanese validation and Korean national cohorts.ConclusionsOur modification of the original GAP model showed improved performance in East-Asian IPF patient populations.     

Serum S100A8 and S100A9 as prognostic biomarkers in acute exacerbation of idiopathic pulmonary fibrosis

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a devastating and life-threatening condition during its clinical course. Biomarkers for precisely anticipating the prognosis of AE-IPF remain to be fully established. The objective of this study was to clarify whether S100A8 and S100A9, which are calcium-binding proteins mainly produced by activated neutrophils, are significant prognostic biomarkers in AE-IPF.MethodsThirty-seven patients with AE-IPF who were diagnosed and treated at our hospital were retrospectively evaluated. The serum levels of S100A8 and S100A9 were measured using enzyme-linked immunosorbent assay, and the relationships between these levels and clinical parameters or prognosis were evaluated.ResultsThe serum levels of S100A8 (median 386.5 ng/mL) and S100A9 (median 60.2 ng/mL) in patients with AE-IPF were significantly higher than those in age-matched healthy controls and in patients at IPF diagnosis (p < 0.001 for all combinations). The serum levels of S100A8 negatively correlated with percent forced vital capacity (r = −0.356, p = 0.049) and positively correlated with peripheral white blood cell number (r = 0.509, p = 0.002). Immunohistochemical staining of autopsy lung specimens showed that neutrophils, present mainly in the alveolar septum, were positive for S100A8 and S100A9. Patients with AE-IPF with higher levels of S100A8 or S100A9 showed significantly worse 3-month survival than those with lower levels (log-rank test, both p = 0.028). Finally, in multivariate analysis, the serum levels of both S100A8 and S100A9 were significant prognostic factors (hazard ratio 4.032, p = 0.023 and hazard ratio 4.327, p = 0.012).ConclusionThe serum levels of S100A8 and S100A9 at AE were significant prognostic biomarkers in patients with AE-IPF.     

Exhaled nitric oxide: A biomarker for chronic obstructive pulmonary disease

The fractional concentration of exhaled nitric oxide (FeNO) is recognized as a biomarker of type 2 inflammation in asthma, which is related to airway eosinophilia. We conducted a prospective observational study in a cohort of Japanese patients with chronic obstructive pulmonary disease (COPD) to evaluate the relationship between FeNO and clinical features and patient outcomes over a 3-year period. Participants were categorized into two groups based on FeNO levels (high and low), and the clinical features and outcomes were compared between the groups. Patients with high FeNO levels showed features of asthma and eosinophilic inflammation compared to those with low levels. However, high FeNO levels were not associated with worse outcomes (exacerbations, hospital admissions, all-cause and disease-specific mortality) compared to low levels. These results provide evidence that baseline FeNO is related to eosinophilic inflammation; however, is not a predictor of future exacerbations or prognosis in patients with stable COPD.     

Effect of pulmonary rehabilitation programs including lower limb endurance training on dyspnea in stable COPD: A systematic review and meta-analysis

Pulmonary rehabilitation (PR) is recommended as an effective treatment for patients with chronic obstructive pulmonary disease (COPD). Previous meta-analyses showed that PR improves exercise capacity and health-related quality of life (HRQOL). However, they did not evaluate the effect of PR on the sensation of dyspnea.We searched six databases in May 2019 for randomized controlled trials (RCTs) that examined PR, including supervised lower limb endurance training as a minimal essential component that was continued for 4–12 weeks, in patients with stable COPD, with changes from baseline dyspnea as a primary outcome. Secondary outcomes were changes in exercise capacity, HRQOL, activity of daily life (ADL), physical activity (PA), and adverse events. We calculated the pooled weighted mean difference (MD) using a random effects model. We identified 42 studies with 2150 participants. Compared with the control, PR improved dyspnea, as shown using the British Medical Research Council (MRC) questionnaire (MD, −0.64; 95% CI, −0.99 to −0.30; p = 0.0003), transitional dyspnea index (MD, 1.95; 95% CI, 1.09 to 2.81; p = 0.0001), modified Borg score during exercise (MD, −0.62; 95% CI, −1.10 to −0.14; p = 0.01), and Chronic Respiratory Questionnaire (CRQ) dyspnea score (MD, 0.91; 95% CI, 0.39 to 1.44; p = 0.0007). PR significantly increased exercise capacity measured by the 6 min walking distance time, peak workload, and peak VO₂. It improved HRQOL measured by the St. George's Respiratory Questionnaire and CRQ, but not on PA or ADL. These results indicated that PR programs including lower limb endurance training improve dyspnea, HRQOL, and exercise capacity in patients with stable COPD.     

Interleukin-37 gene polymorphism and susceptibility to pulmonary tuberculosis among Iraqi patients

BackgroundControl of tuberculosis (TB) depends on a balance between host's immune factors and bacterial evasion strategies. Interleukin-37 (IL-37) is among the immunomodulatory factors that have been proposed to influence susceptibility to tuberculosis.MethodsA case–control study was conducted on 105 patients with pulmonary TB (37 active, 41 multi-drug resistant and 27 relapse) and 79 healthy controls to determine serum levels and single nucleotide polymorphisms (SNPs) of IL-37. The IL-37 level was assessed with an enzyme-linked immunosorbent kit, while DNA-sequencing was used to detect SNPs in the promoter region of IL37 gene.Results: Median level of IL-37 was markedly increased in serum of TB patients compared to controls (325.0 vs. 169.1 pg/mL; p < 0.001). This increase was universally determined in subgroups of patients distributed according to gender, age groups, and clinical type of disease, while no significant differences were found between the subgroups in patients or controls. Analysis of receiver operating characteristic curve confirmed these findings and IL-37 occupied a very good area under the curve, which was 0.816 (95% CI = 0.744–0.888; p < 0.001). At a cut-off value of 185.6 pg/mL, the sensitivity and specificity of IL-37 were 81.0 and 82.3%, respectively. Of the nine detected SNPs (rs2466449 G/A, rs2466450 A/G, rs2723168 G/A, rs3811042 G/A, rs3811045 T/C, rs3811046 G/T, rs3811047 A/G, rs3811048 G/A and rs200782323 G/A), only rs3811048 showed a significant association with TB; the G allele showed a significantly decreased frequency in TB patients compared to controls (25.2 vs. 44.9%; OR = 0.41; p < 0.001). It was possible to assign five haplotypes, and three showed significant differences between patients and controls. Frequency of haplotype A-A-G-A-C-T-G-A-G (0.331 vs. 0.213; OR = 2.10; p = 0.015) was significantly increased in TB patients compared to controls. On the contrary, frequencies of haplotypes A-A-G-A-C-T-G-G-G (0.029 vs. 0.116; OR = 0.24; p = 0.01) and A-A-G-G-T-G-A-G-G (0.140 vs. 0.275; OR = 0.45; p = 0.015) were significantly decreased in patients.ConclusionsIL-37 was up-regulated in the serum of TB patients irrespective of their gender, age or clinical type of disease. SNPs in the promoter region of IL37 gene were proposed to be associated with susceptibility to TB.     

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis

BackgroundAcute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses.MethodsWe investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion.This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan–Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis.ResultsIn this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DL_CO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DL_CO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test).ConclusionsFF and %DL_CO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.     

Thrombolysis with reteplase in acute pulmonary embolism

ObjectiveReteplase (recombinant plasminogen activator) is a mutant of alteplase. It has a longer half-life than its parent molecule and has shown better vessel patency rates in acute myocardial infarction. In this study, we analyzed the efficacy and safety of reteplase in acute pulmonary embolism (PE).MethodsThis observational study included patients with high- and intermediate-risk acute PE, presenting within 14 days of symptom onset. The patients were treated with reteplase, which was given in two bolus doses of 10 U each, 30 min apart, along with intravenous heparin. Patients with hemodynamic compromise (high-risk or massive PE) and normotensive patients with evidence of right ventricular (RV) dysfunction (intermediate-risk or submassive PE) on echocardiography or computed tomography were included in the study. The efficacy outcomes assessed were in-hospital death and improvement of RV function by echocardiography. The safety outcomes were major bleeding, minor bleeding, and ischemic or hemorrhagic stroke during hospitalization.ResultsOf the 40 patients included, 25% were classified as high risk with hemodynamic compromise and 75% were classified as intermediate risk. RV dysfunction was present in all the patients (100%). Concomitant lower extremity deep vein thrombosis was present in 55% of the patients. The mortality rate was 5%. There was significant improvement in RV function and reduction in pulmonary artery systolic pressure and tricuspid regurgitation severity. There was no major bleeding event or stroke, and 7.5% patients had minor extracranial bleeding.ConclusionsDouble-bolus reteplase given with heparin is effective in the treatment of high- and intermediate-risk PE, with minimal risk of bleeding.