Home High-Flow Nasal Cannula Oxygen Therapy for Stable Hypercapnic COPD: A Randomized Clinical Trial.

Rationale: The long-term effects of using a high-flow nasal cannula for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease remain unclear. Objectives: To assess whether long-term high-flow nasal cannula use reduces the number of exacerbations and improves other physiological parameters in patients with chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease. Methods: We enrolled 104 participants (aged ⩾40 yr) with daytime hypercapnia (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) receiving long-term oxygen therapy (⩾16 h/d for ⩾1 mo) and randomly assigned them to high-flow nasal cannula/long-term oxygen therapy and long-term oxygen therapy groups. The primary endpoint was the moderate or severe exacerbation rate. We compared changes from baseline in arterial blood gas values, peripheral oxygen saturation, pulmonary function, health-related quality-of-life scores, and the 6-minute-walk test. Measurements and Main Results: High-flow nasal cannula use significantly reduced the rate of moderate/severe exacerbations (unadjusted mean count 1.0 vs. 2.5, a ratio of the adjusted mean count between groups [95% confidence interval] of 2.85 [1.48-5.47]) and prolonged the duration without moderate or severe exacerbations. The median time to first moderate or severe exacerbation in the long-term oxygen therapy group was 25 (14.1-47.4) weeks; this was not reached in the high-flow nasal cannula/long-term oxygen therapy group. High-flow nasal cannula use significantly improved health-related quality of life scores, peripheral oxygen saturation, and specific pulmonary function parameters. No safety concerns were identified. Conclusions: A high-flow nasal cannula is a reasonable therapeutic option for patients with stable hypercapnic chronic obstructive pulmonary disease and a history of exacerbations. Clinical trial registered with www.umin/ac.jp (UMIN000028581) and www.clinicaltrials.gov (NCT03282019).

Clinical features of relapsed connective tissue disease-associated organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) is recognized as a nonspecific lung injury response characterized histopathologically by the presence of intra-alveolar buds of granulation tissue. Most OP patients show excellent responses to corticosteroids, but relapse is frequently seen when corticosteroids are tapered or discontinued. Although several factors associated with relapse have been reported in cryptogenic OP (COP), the clinical features and risk factors associated with relapse in connective tissue disease-associated OP (CTD-OP) have yet to be fully understood. METHODS: We retrospectively reviewed data on 47 CTD-OP patients. We investigated the frequency of relapse and compared the clinical data between CTD-OP with and without relapse to clarify the risk factors for relapse. RESULTS: Eleven (23.4%) CTD-OP patients had relapses of OP during the study. In the multivariate analysis, no CTD treatment at OP diagnosis [O.R. 11.920, p = 0.012] and partial remission after steroid treatment [O.R. 35.944, p = 0.045] were independent risk factors for relapse. Among rheumatoid arthritis-associated OP (RA-OP) patients, partial remission after steroid treatment [O.R. 16.151, p = 0.047] and age at OP diagnosis [O.R. 0.899, p = 0.045] were independent risk factors for relapse. Most of the relapsed OP patients who were on no medication at OP diagnosis later developed CTD. CONCLUSION: CTD-OP patients with residual disease on HRCT after treatment and who had OP diagnosis preceding CTD diagnosis were more likely to have an OP relapse. During the clinical course of relapsed OP patients, it is necessary to pay attention to the onset of CTD.

Detection of impaired gas exchange using the 1-minute sit-to-stand test in patients with interstitial lung disease.

BACKGROUND: Although pulmonary function tests (PFTs) are important in patients with interstitial lung disease (ILD), they cannot be easily performed in a primary healthcare setting. This study aimed to examine the usefulness of the difference between pulse oxygen saturation (SpO2) at rest and the lowest SpO2 during the 1-min sit-to-stand test (delta SpO2-1STST) for predicting pulmonary function impairment. METHODS: We retrospectively reviewed 116 patients with ILD who underwent 1STST and PFTs. RESULTS: The delta SpO2-1STST and diffusing capacity for carbon monoxide (DLco) strongly correlated (ρ = 0.70). The delta SpO2-1STST was effective in predicting impaired gas exchange (cut-off value, -4%; AUC, 0.86; sensitivity, 74%; specificity, 87%). CONCLUSIONS: The Delta SpO2-1STST may be a reasonable tool for predicting abnormalities in PFTs.

Impact of extrapulmonary comorbidities on physical activity in chronic obstructive pulmonary disease in Japan: A cross-sectional study.

Physical activity, which can be affected by airflow limitation and extrapulmonary comorbidities, has been reported to be reduced in patients with chronic obstructive pulmonary disease, and reduced physical activity is associated with higher risks of exacerbation and mortality. The aim of the present study is to elucidate the comprehensive effect of extrapulmonary comorbidities on physical activity in Japanese patients with chronic obstructive pulmonary disease, of which evidence is lacking. We conducted a cross-sectional study with a series of tests, including lung function, physical activity, symptom scores, and parameters for comorbidities. Sixty outpatients with stable disease were enrolled, and the relationship between the parameters and physical activity was evaluated. Physical activity was assessed over 7 consecutive days using a triaxial accelerometer, which records total daily energy expenditure, step count, and walking time. Cardiovascular status was assessed via echocardiography, and pulmonary artery pressure was estimated using Doppler sonography. As to mental status, depression and anxiety were assessed using the Self-Rating Depression Scale and State-Trait Anxiety Inventory, respectively. Physical activity level was significantly correlated with step count, walking time, body mass index, lean body mass index, lung function, pulmonary artery pressure, depression, anxiety, and serum total cholesterol level. In a median regression model analysis, low lung function, low lean body mass index, depression, and low serum total cholesterol level were independently associated with decreased physical activity level. These findings suggest that physical inactivity is affected by multiple extrapulmonary factors, including skeletal muscle dysfunction, depressive symptoms, and nutritional state, in Japanese patients with chronic obstructive pulmonary disease.

Rapid development and rupture of a pneumatocele caused by pulmonary dissection in the early postoperative period of lung resection: a case report.

Air leakage after lung resection is a common complication usually caused by direct injury to the lung parenchyma. Herein we illustrate a case of pneumatocele that developed rapidly in the right middle lobe and ruptured 16 days after right upper lobectomy. A 73-year-old man with chronic obstructive pulmonary disease underwent thoracoscopic right upper lobectomy and partial thymectomy for primary lung cancer and thymic nodules, respectively. Although a small amount of air leakage was observed after the operation, air leakage completely improved on postoperative day (POD) 2, and the chest drain tube was removed on POD 3. The patient's condition was complicated with eosinophilic pneumonia. Steroid therapy was started on POD 13. Dyspnea suddenly developed immediately after defecation on POD 16. Computed tomography (CT) scan showed a large pneumatocele in the right middle lobe, which was not found by CT scan on POD 11. He underwent reoperation on POD 20, and a large thick-walled pneumatocele in the right middle lobe was directly sewn. Histopathologically, the wall of bulla consisted of thickened visceral pleura and thin lung parenchyma, suggesting that this pneumatocele was induced by dissection of subpleural lung parenchyma.

Clinicopathological feature of a resected large mixed squamous cell and glandular papilloma: A case report.

INTRODUCTION AND IMPORTANCE: Solitary endotracheal papilloma is a rare benign lung tumor. It is classified into the following three histological subtypes: squamous cell papilloma (SP), glandular papilloma (GP), and mixed squamous cell and glandular papilloma (MSGP). MSGP is the rarest among them. Herein, we describe a case of a large MSGP. CASE PRESENTATION: A 59-year-old woman underwent computed tomography for the examination of cough, and an 8.2-cm-sized lung mass was noted in the left lingual segment. Bronchoscopy revealed that the left B5 lumen was completely occluded by a tumor. Transbronchial lung biopsy suggested GP; thereafter, a left upper lobectomy was performed. Macroscopic findings showed that the dilated B5 lumen was filled with cauliflower-like tumors. Histopathological findings showed that the majority of the tumors had pseudostratified columnar epithelium, while some had stratified squamous epithelium. The patient was diagnosed with MSGP. Although koilocytosis-like changes, such as perinuclear halo and nuclear deformation, were observed in some portions of the squamous epithelium, immunohistochemical staining was negative for human papillomavirus (HPV). CLINICAL DISCUSSION: HPV infection is reportedly associated with SP but not with GP and MSGP. Therefore, MSGP is considered to be caused by squamous metaplasia of a part of GP; this hypothesis is consistent with the present case. However, only one case of MSGP with HPV infection was recently reported, and the etiology and histological features of MSGP remain unclear. CONCLUSION: There are few reported cases of MSGP, and further case reports are needed to clarify its pathogenesis.

Clinical features of acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: Comparison with idiopathic pulmonary fibrosis.

BACKGROUND: Several studies have reported that acute exacerbation (AE), which occurs during the clinical course of idiopathic pulmonary fibrosis (IPF), also occurs in rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, the incidence, clinical features, and risk factors for AE, a major cause of death of RA-ILD patients, and the differences in clinical aspects of AE between RA-ILD and IPF have yet to be fully understood. METHODS: We retrospectively reviewed data on 149 RA-ILD patients and 305 IPF patients. We investigated the frequency of AE and compared the clinical data between RA-ILD with and without AE to clarify the risk factor for AE. We also compared the post-AE prognosis and cause of death between RA-ILD and IPF patients. RESULTS: Twenty-seven (18.1%) RA-ILD patients and 84 (27.5%) IPF patients developed AE. The median survival time (MST) after AE of RA-ILD and IPF was 277 days and 60 days, respectively (log rank, p = 0.038). In a multivariate analysis, hypoalbuminemia [odds ratio (O.R.) 0.090 (95%CI 0.011-0.733), p = 0.012] and % carbon monoxide diffusion capacity (%DLCO) [O.R. 0.810 (95%CI 0.814-0.964), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death of RA-ILD and IPF. CONCLUSION: RA-ILD patients could develop AE, and AE was not uncommon in RA-ILD or IPF. %DLCO and hypoalbuminemia were predictive factors of AE in RA-ILD. The prognosis after AE of RA-ILD was significantly better than that of IPF. The most frequent cause of death in RA-ILD and IPF was AE.

Acute exacerbation in antineutrophil cytoplasmic antibody-associated interstitial lung disease: Clinical features and risk factors.

BACKGROUND: Acute exacerbation (AE) is a life-threatening clinical event that occurs during the clinical course of idiopathic pulmonary fibrosis (IPF). Several studies have reported that AE also occurs in interstitial lung disease (ILD) other than IPF. However, the incidence, clinical features, risk factors for AE, and major causes of death in antineutrophil cytoplasmic antibody (ANCA)-associated ILD (ANCA-ILD) patients have not been well established. METHODS: We retrospectively reviewed the data of 54 ANCA-ILD patients and 304 IPF patients. We investigated the frequency of AE, post-AE prognoses, risk factors for AE, and major causes of death in ANCA-ILD patients. We also compared the data of ANCA-ILD with that of IPF. RESULTS: Fourteen (25.9%) ANCA-ILD patients and 84 (27.6%) IPF patients developed AE. The median survival times (MSTs) after AE in ANCA-ILD and IPF patients were 35.5 and 60 days, respectively (p = 0.588, log-rank test). In a multivariate analysis, the percentage of predicted forced vital capacity (%FVC) [O.R. 0.750 (95% CI 0.570, 0.986), p < 0.01] and serum C-reactive protein (CRP) [O.R. 2.202 (95% CI 1.037, 4.674), p < 0.01] were independent risk factors for AE. AE was the most frequent cause of death in ANCA-ILD and IPF patients. CONCLUSION: ANCA-ILD patients could develop AE, and the frequency of AE in ANCA-ILD is similar to that in IPF. AE is the most frequent cause of death in ANCA-ILD patients. A low %FVC and a high serum CRP level were independent predictive factors for AE in ANCA-ILD. The prognosis after AE in ANCA-ILD was poor, as it was in IPF.

The 1-minute sit-to-stand test to detect desaturation during 6-minute walk test in interstitial lung disease.

Although the 6 min walk test (6MWT) is well-established for assessing desaturation in patients with interstitial lung disease (ILD), it cannot be easily performed in primary healthcare settings. This retrospective observational study aimed to evaluate the usefulness of the 1 min sit-to-stand test (1STST) for assessing desaturation during 6MWT in ILD patients with normal resting blood oxygen levels. We included 116 patients, and the pulse oxygen saturation (SpO2) for both methods was analyzed. The SpO2 nadir during the 1STST and 6MWT correlated strongly (ρ = 0.82). The frequency of patients with nadir SpO2 < 90% was consistent for both tests (κ = 0.82). 1STST was superior to diffusing capacity for carbon monoxide in detecting desaturation during the 6MWT. These findings were similarly stratified according to performance status or dyspnea scale. The 1STST can easily measure exertional desaturation in ILD patients with normal resting blood oxygen levels and is an alternative to the 6MWT.

[Chronological change of primary type pulmonary Mycobacterium avium-intracellulare complex infection].

OBJECTIVES: Primary pulmonary Mycobacterium avium-intracellulare complex (MAC) disease was evaluated from the viewpoint of chronological change. METHOD: From 1993 to March 2009, 130 patients with primary-type MAC disease were divided into three groups according to the period of time when they were diagnosed as below, and compared between groups by retrospective review. RESULTS: Average numbers of cases per year were 5.12 patients in the 1st period (from 1993 to 2002), 10.98 in the 2nd period (from 2002 to 2006), 15.87 in the 3rd period (from 2006 to 2009). The number of cases per year gradually increased with time, while the percentage of females gradually decreased with time (84.1%, 74.4%, 69.8% for each period, p < 0.05). Patient BMIs (body mass indexes) showed an upward trend while CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) showed downward trends though these changes were not significant. CONCLUSION: Though primary-type MAC disease typically affects mid-elderly and slender women, the authors demonstrated that it is increasing among male and non-slender females. Changes in the clinical features of primary-type MAC disease over time were also observed.

[Analysis of endobronchial aspergillosis in patients without obvious systemic predisposing factors].

BACKGROUND: Endobronchial aspergillosis is still an insufficiently recognized concept. PATIENTS AND METHODS: Ten patients who did not have obvious predisposing factors and parenchymal fungal infection were analyzed. They were confirmed to have endobronchial Aspergillus by histology and culture, and were classified according to the presence of bronchiectasis, allergic reaction, and asthmatic symptom. RESULTS: Bronchiectasis was detected in all 10 patients, IgE elevation (>370 IU/ml) in 7, Aspergillus specific IgE-RAST in 8, eosinophilia in 7, and asthmatic symptom in 5. Cases were classified into allergic bronchopulmonary aspergillosis (ABPA) (5 cases), ABPA not fulfilling Rosenberg's criteria (2 cases), and endobronchial aspergilloma (3 cases). CONCLUSION: We proposed classifying endobronchial aspergillosis without obvious systemic predisposing factors into "ABPA", "ABPA without asthma", "ABPA-S (seropositive)", and "Endobronchial aspergilloma". A fifth subtype of endobronchial aspergillosis containing "saprophyte" is warranted.

Nicotine Induces Resistance to Erlotinib Therapy in Non-Small-Cell Lung Cancer Cells Treated with Serum from Human Patients.

Previously, we reported that nicotine reduces erlotinib sensitivity in a xenograft model of PC9, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-sensitive non-small-cell lung cancer cell line. The present study examined whether smoking induces erlotinib resistance in vitro. We assessed resistance to EGFR-TKIs by treating cancer cell lines with erlotinib, afatinib, or osimertinib, and serum collected from smokers within 30 min of smoking and that from a non-smoker as a control. We also assessed erlotinib resistance by treating PC9 cells exposed to serum from a smoker or a non-smoker, or serum from an erlotinib user. Treatment of the cancer cell lines with serum from smokers induced significant erlotinib resistance, compared with the control (p < 0.05). Furthermore, serum samples with a high concentration of cotinine (a nicotine exposure indicator) demonstrated stronger erlotinib resistance than those with low concentrations. Similar to the observations with erlotinib treatment of cell lines, the analysis of serum from erlotinib users revealed that smokers demonstrated significantly reduced sensitivity to erlotinib (p < 0.001). In conclusion, our present results support the hypothesis that smoking contributes to resistance to erlotinib therapy in non-small-cell lung cancer.

[Solitary nodular sarcoidosis demonstrating reversed tuberculin skin reaction].

A 29-year-old woman was admitted because of chest radiograph abnormality. She had no respiratory complaints. Chest CT demonstrated an ill-defined nodule of 20mm with the "sarcoid galaxy sign" in the right upper lobe. Transbronchial biopsy (TBB) specimens from right S2 revealed non-caseating epithelioid cell granuloma. Initial clinical findings suggested mycobacterial infection. However, while waiting for the results of mycobacterial cultures in bronchial washing fluid, the tuberculin skin reaction was found to be negative, and enlargement of nodule, mediastinal lymphadenopathy and elevated soluble IL-2R were observed. Cultures for mycobacterium were negative and repeat TBB specimens revealed granulomatous inflammation. We diagnosed with sarcoidosis based on these findings. Solitary nodular sarcoidosis is rare with only 17 cases having been reported. These cases were diagnosed with difficulty because of non-specific clinical findings and of the 17, 16 cases (94%) were diagnosed by surgical procedures. We observed the clinico-radiological course of solitary nodules and the change in tuberculin reaction. Although a negative tuberculin skin reaction was commonly recognized in sarcoidosis patients, we confirmed that initial positive tuberculin reaction changed to negative according to disease progress. To the best of our knowledge, this is the first case report in adults.

[Bird-related chronic hypersensitivity pneuminitis demonstrating the fluctuation of disease activity accompanied with environmental changes].

We report a case of bird-related chronic hypersensitivity pneuminitis exhibiting the fluctuation of serum markers for interstitial lung disease along with the changes in life environment. A 65-year-old man had had an abnormal chest radiograph for 2 years and had complained of a non-productive cough. He had had 30 parakeets 20 years previously and had used feather products for 15 years. In autumn and early winter wild birds had visited persimmons trees in the neighboring garden. Antibodies to bird-related antigens in the broncho-alveolar lavage fluids and sera were positive and the thoracoscopic lung biopsy specimens histologically revealed airway-centered fibrosis. We then determined he was having bird-related chronic hypersensitivity pneumonitis. After avoidance of feather products, all of serum SP-A, SP-D and KL-6 decreased. But three markers elevated and radiographic findings worsened accompanied with the increase of visiting wild birds in next autumn. After pruning persimmon trees and starting corticosteroid with cyclosporine, disease activity gradually improved.

[Case of metastatic germ cell tumor with testicular calcification detected by MD-CT].

Metastasis of testicular germ cell tumor should be included in the differential diagnosis when young male patient have multiple pulmonary metastases. However burned-out tumors cannot be easily detected on inspection and palpation of the testis. A 19 year-old man visited to our hospital complaining of anorexia, weight loss and dyspnea. Chest X-ray films showed multiple lung nodules. Physical examination revealed gynecomastia, and many cervical, axillary, and inguinal lymph nodes with a diameter of 1 cm were palpable. Physical examination of testis revealed no laterality. Multi-detector CT showed multiple lung nodules, a hepatic and a retroperitoneal large mass and a tiny calcification in the right testis. Histological findings of the lung obtained by percutaneous biopsy and the presence of a calcification in the testis led to a diagnosis of testicular choriocarcinoma showing burned-out tumor. However there was no previous report of burned-out tumor detected by CT, MD-CT including that of the testis was valuable at the first diagnostic stage when germ cell tumor was suspected.

[A case of radiographic stage 0 sarcoidosis with severe cough].

A 63-year-old woman complained of continuous dry cough and high fever for two months. Chest radiography showed no abnormality, but inspiratory fine crackles were audible. Interstitial lung disease was suspected and bronchoalveolar lavage was performed via a bronchoscope. Disseminated minute granular lesions with redness and hypervascularity from the upper trachea to bilateral lober bronchi were detected. Lesions were also present in the membranous portion of the left main bronchus. Histological results for bronchial biopsy and transbronchial lung biopsy showed non-caseous epithelioid cell granuloma. This, together with a high CD4/8 lymphocyte ratio (4.11) in bronchoalveolar lavage fluid and the gallium scintigraphic findings, confirmed the diagnosis of sarcoidosis. To the best of our knowledge there are no other reports of cases with a similar bronchoscopic appearance in which the chest roentgenologic classification was stage 0, despite severe respiratory symptoms. Nodular lesions are seen in some cases of endobronchial sarcoidosis, but in this case, these widespread granular lesions were a unique feature that prompted us to make this report.

[A case of allergic bronchopulmonary aspergillosis localized in one bronchial segment].

A 64-year-old woman was admitted with a chest radiograph abnormality. She had no compliant and the results of her physical examination were normal. A chest radiograph showed a 25-mm area of patchy opacity in the left upper lung field. Chest CT demonstrated a finger-like opacity along the left B3a and c that was highly suggestive of mucoid impaction of the bronchi. Bronchofiberscopy revealed mucous plugs in left B3, in which the filariform fungul hyphae were detected by Grocott stain. Rosenberg's clinical criteria have been cited frequently for the diagnosis of allergic bronchopulmonary aspergillosis (ABPA). On the one hand his criteria have historical significance, but at the same time various problems have been pointed out. Although the patient was not given a diagnosis of ABPA based on Rosenberg's criteria, she was given it based on the presence of type I immunologic response, mucoid plugs, hyphae of Aspergillus, central bronchiectasis. She had localized opacity only along a segmental bronchus. Our report may provide valuable information on the course of ABPA.