The association between transfer coefficient of the lung and the risk of exacerbation in asthma-COPD overlap: an observational cohort study.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) patients experience exacerbations more frequently than those with asthma or COPD alone. Since low diffusing capacity of the lung for carbon monoxide (DLCO) is known as a strong risk factor for severe exacerbation in COPD, DLCO or a transfer coefficient of the lung for carbon monoxide (KCO) is speculated to also be associated with the risk of exacerbations in ACO. METHODS: This study was conducted as an observational cohort survey at the National Hospital Organization Fukuoka National Hospital. DLCO and KCO were measured in 94 patients aged ≥ 40 years with a confirmed diagnosis of ACO. Multivariable-adjusted hazard ratios (HRs) for the exacerbation-free rate over one year were estimated and compared across the levels of DLCO and KCO. RESULTS: Within one year, 33.3% of the cohort experienced exacerbations. After adjustment for potential confounders, low KCO (< 80% per predicted) was positively associated with the incidence of exacerbation (multivariable-adjusted HR = 3.71 (95% confidence interval 1.32-10.4)). The association between low DLCO (< 80% per predicted) and exacerbations showed similar trends, although it failed to reach statistical significance (multivariable-adjusted HR = 1.31 (95% confidence interval 0.55-3.11)). CONCLUSIONS: Low KCO was a significant risk factor for exacerbations among patients with ACO. Clinicians should be aware that ACO patients with impaired KCO are at increased risk of exacerbations and that careful management in such a population is mandatory.

Impact of visceral fat on the prognosis of coronavirus disease 2019: an observational cohort study.

BACKGROUND: Clarification of the risk factors for coronavirus disease 2019 (COVID-19) severity is strongly warranted for global health. Recent studies have indicated that elevated body mass index (BMI) is associated with unfavorable progression of COVID-19. This is assumed to be due to excessive deposition of visceral adipose tissue (VAT); however, the evidence investigating the association between intra-abdominal fat and COVID-19 prognosis is sparse. We therefore investigated whether measuring the amount of intra-abdominal fat is useful to predict the prognosis of COVID-19. METHODS: The present study enrolled 53 consecutive cases of COVID-19 patients aged ≥ 20 years with chest computed tomography (CT) scans. The VAT area, total adipose tissue (TAT) area, and VAT/TAT ratio were estimated using axial CT images at the level of the upper pole of the right kidney. Severe COVID-19 was defined as death or acute respiratory failure demanding oxygen at ≥ 6 L per minute, a high-flow nasal cannula, or mechanical ventilation. The association of VAT/TAT with the incidence of progression to a severe state was estimated as a hazard ratio (HR) using Cox regression analysis. To compare the prediction ability for COVID-19 disease progression between BMI and VAT/TAT, the area under the receiver operating characteristic curve (AUC) of each was assessed. RESULTS: A total of 15 cases (28.3% of the whole study subjects) progressed to severe stages. The incidence of developing severe COVID-19 increased significantly with VAT/TAT (HR per 1% increase = 1.040 (95% CI 1.008-1.074), P = 0.01). After adjustment for potential confounders, the positive association of VAT/TAT with COVID-19 aggravation remained significant (multivariable-adjusted HR = 1.055 (95% CI 1.000-1.112) per 1% increase, P = 0.049). The predictive ability of VAT/TAT for COVID-19 becoming severe was significantly better than that of BMI (AUC of 0.73 for VAT/TAT and 0.50 for BMI; P = 0.0495 for the difference). CONCLUSIONS: A higher ratio of VAT/TAT was an independent risk factor for disease progression among COVID-19 patients. VAT/TAT was superior to BMI in predicting COVID-19 morbidity. COVID-19 patients with high VAT/TAT levels should be carefully observed as high-risk individuals for morbidity and mortality.

Association of serum antibodies against the Mycobacterium avium complex and hemoptysis: a cross-sectional study.

BACKGROUND: Hemoptysis is very common and can be life threatening in clinical practice for nontuberculous mycobacteria. The serum antibody against the Mycobacterium avium complex (MAC-Ab), the majority of nontuberculous mycobacteria species, is well known to reflect the activity of MAC lung disease; however, there is no study investigating the association between the MAC-Ab and hemoptysis in MAC patients. Therefore, we assessed whether the MAC-Ab is a good biomarker for hemoptysis among subjects with MAC lung disease. METHODS: This study was conducted as a five-year retrospective survey at the National Hospital Organization Fukuoka National Hospital. A total of 155 patients aged ≥20 years with MAC lung disease were enrolled and separated into seropositive and seronegative groups using the cutoff for MAC-Ab levels of 0.7 U/ml. The prevalence of hemoptysis and odds ratios for the presence of hemoptysis were estimated and compared between the groups. To investigate the linear trends in the relationship between MAC-Ab levels and hemoptysis, the subjects were classified into three groups using the tertile distribution of the MAC-Ab. RESULTS: The prevalence of hemoptysis was twice as high in the seropositive group than in the seronegative group (42.2 and 21.7%, respectively, P = 0.02). The multivariable-adjusted risk of hemoptysis was elevated in the seropositive group as compared with the seronegative group (odds ratio = 2.79 (95% confidence interval 1.15-7.44)). Likewise, when categorizing the subjects into three groups, the risk of hemoptysis increased with increasing MAC-Ab levels (P = 0.03 for trend). CONCLUSIONS: A positive MAC-Ab level was a significant risk factor for hemoptysis among patients with MAC lung disease. There were also positive trends in the association between the MAC-Ab titer and the likelihood of hemoptysis. Measuring the MAC-Ab may contribute not only to early detection of the risk of hemoptysis but also to early intervention with anti-NTM therapy and, as a result, to the prevention of hemoptysis in MAC patients.

Effects of tiotropium on lung function in current smokers and never smokers with bronchial asthma.

The effects of tiotropium, an inhaled long-acting muscarinic antagonist, on lung function were investigated in current smokers and nonsmokers with asthma treated with inhaled corticosteroids (ICSs) and other asthma controllers: inhaled long-acting ß2 agonists, leukotriene receptor antagonists, and/or theophylline. We conducted a double-blind, placebo-controlled study of an inhaled single dose of tiotropium in 9 asthmatics currently smoking and 9 asthmatics who have never smoked in a crossover manner. Lung function was measured before and 1, 3, and 24 h after inhalation of 18 µg of tiotropium or a placebo. The primary outcome was a change in forced expiratory volume in 1 s (FEV1) from the baseline, and the secondary outcomes were changes in peak expiratory flow rate (PEFR), V˙50, and V˙25. At baseline, asthmatics with and without a smoking history had a mean FEV1 of 2590 ml and 2220 ml and were taking a mean dose of ICSs of 1208 and 1000 µg/day, respectively. The increase from the baseline FEV1 was 169 ml and 105 ml higher at 3 h after tiotropium than after the placebo in current smokers and nonsmokers, respectively. PEFR, V˙50, and V˙25 were also significantly increased after tiotropium as compared with the placebo in both study groups. Changes in FEV1 and PEFR tended to be greater in asthmatics currently smoking than in subjects who have never smoked, although there were no statistical differences at any time points. Tiotropium resulted in improved lung function and symptoms both in current smoker and nonsmoker asthmatics. These findings suggest that tiotropium will provide a new strategy for the treatment of bronchial asthma.

Preserved ratio impaired spirometry and severity of obstructive sleep apnea: An observational cross-sectional study.

BACKGROUND AND OBJECTIVE: Lung function abnormality of obstructive sleep apnea (OSA) has not been explored well. Preserved ratio impaired spirometry (PRISm) is known for its association with obesity and cardiovascular morbidity, which are also characteristic features of OSA. This study aims to investigate whether the prevalence of PRISm increases according to apnea-hypopnea index levels among subjects with OSA. METHODS: Conducted as an observational cross-sectional study, the study included 372 patients ≥40 years of age with definitive diagnoses of OSA and pulmonary function assessment from 2000 to 2004. Study subjects were classified based on OSA severity (mild/moderate versus severe). The prevalence of PRISm was estimated and compared between mild/moderate and severe OSA groups. RESULTS: The prevalence of PRISm was 9.4 % in study subjects, with a higher prevalence in the severe OSA group than the mild/moderate group (12.9 % and 6.2 %, respectively, P = 0.04). The positive association between severe OSA and PRISm remained robust after multivariable adjustment for age, gender, and obesity (multivariable-adjusted odds ratio 2.29 (95 % confidence intervals 1.08-4.86), P = 0.03). CONCLUSION: Severe OSA is an independent risk factor for PRISm, highlighting the need for comprehensive management of OSA that addresses the potential risk of PRISm.

Relapsing eosinophilic pneumonia in a patient with recurrent breast cancer receiving abemaciclib plus endocrine therapy.

This report presents the case of a 42-year-old Japanese woman with recurrent hormone receptor-positive breast cancer who developed eosinophilic pneumonia (EP) during treatment with abemaciclib combined with endocrine therapy. Seven years after a radical surgery and definite diagnosis of Stage I breast cancer, her cancer recurred with metastases to multiple organs. Initially treated with abemaciclib plus letrozole and goserelin for 3 months, she developed EP, which improved after the discontinuation of anti-cancer treatment and the administration of prednisolone. However, EP occurred again upon the reintroduction of endocrine therapy (i.e., letrozole and goserelin). It improved gradually with the suspension of endocrine therapy and the re-administration of prednisolone. This case underscores the need for further research into the prevention and management of EP in patients receiving abemaciclib with endocrine therapy for advanced breast cancer.

Acute Exacerbation of Idiopathic Pulmonary Fibrosis With Concurrent Cardiac Amyloidosis: A Technetium Pyrophosphate Study.

Amyloidosis presents a diagnostic challenge, particularly when concomitant with severe conditions like acute exacerbations of idiopathic pulmonary fibrosis (IPF). In this report, we detail the case of a 73-year-old patient with acute exacerbation of IPF and simultaneous emergence of cardiac amyloidosis. The patient's clinical journey began with persistent exertional dyspnea, progressing to hypoxemia on admission. Chest CT scans showed extensive ground-glass opacities, consolidations, and pre-existing honeycombing-like cysts and reticular shadows, accompanied by a right-sided pleural effusion. The therapeutic strategy for acute exacerbation of IPF encompassed methylprednisolone pulse therapy, tacrolimus, and nintedanib, augmented with intravenous immunoglobulin and recombinant thrombomodulin. Concurrently, heart failure with preserved ejection fraction was managed with a pharmacological trio: empagliflozin, diuretics, and eplerenone. A hypertrophied heart and low limb voltage prompted an investigation for cardiac amyloidosis, which 99mTechnetium pyrophosphate (99mTc-PYP) scintigraphy confirmed, yielding a probable diagnosis. Following steroid tapering, the patient was discharged home. This case prompted an investigation into the potential role of amyloidosis in pulmonary pathology. Our retrospective review of 10 patients, including four with cardiac amyloidosis, who underwent 99mTc-PYP scintigraphy, revealed a nonsignificant yet notable trend of increased pulmonary accumulation in cardiac amyloidosis cases (median (interquartile range): 5.4×104 (5.3-13.1×104) vs. 3.6×104 (2.4-5.1×104), p=0.0667). Notably, the pulmonary counts in this patient exceeded the negative cohort's mean values, hinting at a possible contribution of amyloid deposition to pulmonary pathology. This study, pioneering in evaluating lung field accumulation of 99mTc-PYP in cardiac amyloidosis, may provide novel insights into the influence of amyloidosis on pulmonary conditions.

A Case of Pneumocystis Pneumonia Developed During Rheumatoid Arthritis Treatment With Methotrexate and Golimumab.

Here, we report a case of an 87-year-old female patient with rheumatoid arthritis (RA) treated with methotrexate (MTX) and golimumab who developed severe pneumocystis pneumonia (PCP), also known as Pneumocystis jirovecii pneumonia. The patient presented with chief complaints of dyspnea on exertion, dry cough, and fatigue. A high-resolution chest CT scan revealed diffuse, unevenly distributed ground-glass opacities throughout both lungs. The patient was clinically diagnosed with PCP based on the clinical settings, imaging, and a high level of serum ß-D-glucan. While the patient required high-flow oxygen therapy, low-dose trimethoprim/sulfamethoxazole and corticosteroid therapy improved her condition, and the patient was discharged on day 25. Although to our knowledge no case report has been published regarding PCP in patients with RA treated with golimumab, this case emphasizes the importance of attention to opportunistic infections in elderly patients receiving immunosuppressive therapy. MTX use alongside tumor necrosis factor inhibitors like golimumab may increase the risk of serious infections such as PCP. The case underscores the necessity of prophylactic measures and early intervention for PCP, highlighting the delicate balance between immunosuppression benefits and infection risks in RA management.

Effective treatment of inhaled corticosteroid and bronchodilator for "lymphocytic interstitial pneumonia" in primary Sjögren's syndrome.

We present a case of an 86-year-old woman who visited our hospital with a one-year history of exertional dyspnea (modified medical research council dyspnea scale; mMRC grade 2). Despite the absence of any smoking or dust exposure history, multiple cystic lesions were apparent in both lungs on her CT scan. We suspected Sjögren's syndrome-associated lymphocytic interstitial pneumonia (LIP) due to her additional symptoms of dry mouth and eyes. Her respiratory function test showed a restrictive disorder with a forced vital capacity (FVC) of 1.23 L (70.3 % predicted), forced expiratory volume in 1 s (FEV1) of 0.88 L, and FEV1/FVC of 71.5 %. The flow-volume curve showed a downward convex, suggesting peripheral airway obstruction. We initiated a daily inhalation treatment regimen comprising vilanterol 25 µg and fluticasone furoate 200 µg. One month later, at the follow-up visit, the clinical diagnosis of Sjögren's syndrome with LIP was made by positive SS-A and SS-B antibodies in the initial blood work, a Saxon test that confirmed decreased salivary secretion, and a confirmed diagnosis of dry eyes by her ophthalmologist. We noted improvement in FVC of 1.45 L (+17.8 %) and FEV1 to 0.99 L (+12.5 %) in the subsequent respiratory function test, along with alleviation of her symptoms. The present case represents the first report of LIP treated exclusively with inhaled corticosteroids and bronchodilators, highlighting a potential therapeutic approach, particularly for elderly patients vulnerable to immunosuppressive therapies.

Amikacin Liposome Inhalation Suspension in the Real-World Management of Refractory Mycobacterium avium Complex Pulmonary Disease.

The increasing prevalence of Mycobacterium avium complex (MAC) pulmonary disease poses a significant therapeutic challenge, particularly due to the limited efficacy and systemic toxicity associated with conventional guideline-based therapy. Amikacin liposome inhalation suspension (ALIS) has been developed, yet its real-world application remains underreported. This retrospective analysis, conducted from March 2021 to February 2024, examined ALIS's clinical use in patients aged 20 years or older with refractory MAC pulmonary disease at our institution. The primary objective of this study is to describe the patient characteristics and clinical trajectories associated with the initiation of ALIS therapy in real-world settings for individuals diagnosed with MAC pulmonary disease. Of 11 patients initiated on ALIS, one was excluded due to financial constraints impacting continuation. The analysis proceeded with the remaining 10 subjects. The mean age of participants was 70.2 years, with a predominance of female patients (n = 7, 70%) and a higher incidence of M. avium infections (n = 6, 60%). Forty percent of the cohort (n = 4) had a history of ethambutol-induced optic neuritis leading to the cessation of the drug. The average interval from the initiation of guideline-based therapy to the start of ALIS was 8.5 ± 6.9 years (mean ± standard deviation). The majority (80%) presented with positive Gaffky scores at ALIS initiation, and a significant proportion exhibited resistance to clarithromycin and ethambutol. Comorbid conditions, including diabetes and previous cancer, were noted. The study also observed elevated anti-MAC antibody levels. Treatment duration varied, with fatigue leading to discontinuation in two cases. Treatment-emergent adverse events were documented in individual patients, each presenting with grade 1 severity: hemoptysis (n = 1, 10%), elevated creatinine levels (n = 1, 10%), and dysphonia (n = 2, 20%) were observed, respectively. Correlation analysis revealed a significant inverse relationship between body mass index (BMI) and ALIS discontinuation due to fatigue, and a positive correlation between Gaffky scores and C-reactive protein (CRP) levels. These results underscore the potential benefits and limitations of ALIS, suggesting that timely intervention and comprehensive healthcare support are crucial for optimal outcomes in the treatment of advanced MAC pulmonary disease.

Acute Pneumonitis Associated With the Inhalation of Pyrethroid-Based Domestic Insecticides.

We report a 72-year-old female who presented to our hospital with a worsening cough and dyspnea that had emerged a week earlier following the accidental inhalation of a significant quantity of spray-type imiprothrin (a synthetic pyrethroid)-based insecticide in her bathroom. She exhibited acute respiratory failure necessitating 4 L/minute of nasal oxygen at maximum. Chest CT images showed diffuse centrilobular ground-glass opacities with mosaic attenuation and consolidation areas in the lower lobes of both lungs. The patient was diagnosed with acute pneumonitis due to insecticide inhalation, and her symptoms improved following methylprednisolone pulse and alpha-tocopherol therapy. Generally, the accidental inhalation of aerosolized pyrethroids does not induce significant respiratory symptoms, and case reports on pulmonary toxicity related to pyrethroid inhalation are scarce. This case report underscores the need to include inhaled pyrethroid insecticides in the differential diagnosis of patients with acute pneumonitis and suggests that methylprednisolone and alpha-tocopherol therapy can be beneficial for treating this condition.

A Teaching Case: Persistent COVID-19 Pneumonia Resembling Cryptogenic Organizing Pneumonia in a Patient With Remitted Lymphoma.

We report a case of a female patient in her 50s, previously diagnosed with follicular lymphoma (now in complete remission), who was admitted to our hospital due to antibiotic-resistant pneumonia lasting a month. The patient had contracted coronavirus disease 2019 (COVID-19) pneumonia a year earlier and exhibited persistent hypogammaglobulinemia. Chest CT scans revealed wondering ground-glass opacities and consolidations initially suggestive of cryptogenic organizing pneumonia (COP). Despite repeatedly negative nasopharyngeal SARS-CoV-2 tests, the virus was detected in the bronchoalveolar lavage fluid (BALF) using the BioFire FilmArray Respiratory Panel 2.1. She was subsequently diagnosed with COVID-19 pneumonia and responded well to treatment with remdesivir (RDV) and intravenous immunoglobulin. The SARS-CoV-2 variant in the BALF was suspected as the Omicron variant (XBB.1.16), prevalent in the area at the admission, indicating a re-infection rather than a recurrence. This case underscores the protracted nature of COVID-19 pneumonia in immunocompromised patients and the risks of false negatives in nasopharyngeal SARS-CoV-2 tests. Direct SARS-CoV-2 measurement from BALF can be crucial in such cases. A COP diagnosis based solely on imaging and administering corticosteroids without antiviral treatment might exacerbate the situation by reactivating SARS-CoV-2. Given the current pandemic, clinicians should be aware of the potential for persistent or recurrent COVID-19, particularly in immunocompromised patients.

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.

Tezepelumab treatment for allergic bronchopulmonary aspergillosis.

An 82-year-old man had been diagnosed with asthma. He experienced repeated exacerbations requiring treatment with a systemic corticosteroid despite being treated with medications including high-dose fluticasone furoate/umeclidinium/vilanterol, montelukast sodium, and theophylline; treatment with mepolizumab was then initiated. The patient had been free from exacerbations for 15 months; however, he suffered from post-obstructive pneumonia and atelectasis secondary to mucoid impaction in the right middle lobe of the lung, accompanied by a productive cough, wheezing, dyspnea, and right chest pain. In addition to the development of mucus plugs, the levels of serum IgE specific to Aspergillus spp. became positive; a definite diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was established. The patient underwent treatment with tezepelumab. Over 3 months, the mucus plugs and pulmonary opacities diminished gradually in parallel with the improvement in the control of asthmatic symptoms. Tezepelumab might provide a novel steroid-sparing strategy for the management of ABPA, although further studies are required.

Lung sound analysis in a patient with vocal cord dysfunction and bronchial asthma.

OBJECTIVE: Vocal cord dysfunction (VCD) is a condition characterized by adduction of the vocal cords, resulting in narrowing or even closure of the glottis during inspiration. This can cause wheezing that originates at the site of narrowing. Some patients have both VCD and asthma. In such cases, an acute episode of VCD can be difficult to differentiate from that of asthma. We tested the usefulness of lung sound analysis (LSA) in such a condition. METHODS: We performed an LSA in a patient with asthma and coexisting VCD diagnosed using laryngoscopy. RESULTS AND CONCLUSION: The LSA during an acute VCD episode revealed monophonic continuous adventitious sounds that were distributed symmetrically over both lung fields. The time domain analysis revealed that the adventitious sounds originated in the neck. These LSA findings clearly indicated that the acute episode was not due to asthma but due to VCD. This case illustrates that the LSA may be a useful tool to differentiate between an acute episode of asthma and that of VCD.

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.

The Prognostic Performance of Lung Diffusing Capacity in Preserved Ratio Impaired Spirometry: An Observational Cohort Study.

Purpose: Similar to chronic obstructive pulmonary disease (COPD), the diffusing capacity of the lung (DLCO) might be decreased and associated with poor prognosis in preserved ratio impaired spirometry (PRISm), a clinical entity as a prodromal phase of COPD. The aims of the present study were to evaluate the distributions of DLCO and to assess the association between DLCO and mortality among subjects with PRISm. Patients and Methods: We conducted an observational cohort study at the National Hospital Organization Fukuoka National Hospital. We classified the 899 patients ≥ 40 years of age with an assessment of DLCO into five groups based on spirometry: preserved spirometry, PRISm, mild COPD, moderate COPD, and severe/very severe COPD. The prevalence of low DLCO (< 80% per predicted) was compared among the five groups. Using PRISm patients with follow-up data, we further investigated the association of low DLCO with all-cause mortality. Results: The prevalence of low DLCO in the PRISm group (58.8%) was significantly higher than that in the preserved-spirometry group (21.8%), the mild-COPD group (23.5%), and the moderate-COPD group (36.0%) (all P < 0.01), and it was comparable to that in the severe/very severe-COPD group (63.2%). The results remained unchanged after adjusting for potential confounders. Among the PRISm subjects, the overall survival rate was significantly lower in the low-DLCO group than in the preserved-DLCO group (P < 0.01). The multivariable-adjusted hazard ratio (HR) for all-cause mortality was significantly higher in the low-DLCO group than in the preserved-DLCO group (HR = 10.10 (95% confidence interval 2.33-43.89)). Conclusion: Diffusing capacity was more impaired in PRISm subjects than in those with preserved spirometry or mild to moderate COPD. Regarding PRISm, low DLCO was a significant risk factor for all-cause mortality. Clinicians should assess DLCO in the management of PRISm to predict the future risk of overall death.

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.

Nintedanib treatment for pulmonary fibrosis after coronavirus disease 2019.

A 78-year-old Japanese woman with no smoking history suffered from near-fatal coronavirus disease 2019 (COVID-19) requiring four-week invasive mechanical ventilation, with subsequent radiological features of pulmonary fibrosis. Although methylprednisolone gradually improved her respiratory condition, her oxygenation and exercise tolerance had drastically deteriorated, necessitating high-flow nasal cannula oxygen therapy. In parallel with tapering systemic steroid, the patient was treated with nintedanib. Three months later, the patient was able to walk with a walking aid using oxygen at 4 L/min. The present case is an indication that nintedanib might provide a novel therapeutic approach for managing post-COVID-19 fibrosis, although further studies are warranted.

Lung sound analysis helps localize airway inflammation in patients with bronchial asthma.

PURPOSE: Airway inflammation can be detected by lung sound analysis (LSA) at a single point in the posterior lower lung field. We performed LSA at 7 points to examine whether the technique could identify the location of airway inflammation in patients with asthma. PATIENTS AND METHODS: Breath sounds were recorded at 7 points on the body surface of 22 asthmatic subjects. Inspiration sound pressure level (ISPL), expiration sound pressure level (ESPL), and the expiration-to-inspiration sound pressure ratio (E/I) were calculated in 6 frequency bands. The data were analyzed for potential correlation with spirometry, airway hyperresponsiveness (PC20), and fractional exhaled nitric oxide (FeNO). RESULTS: The E/I data in the frequency range of 100-400 Hz (E/I low frequency [LF], E/I mid frequency [MF]) were better correlated with the spirometry, PC20, and FeNO values than were the ISPL or ESPL data. The left anterior chest and left posterior lower recording positions were associated with the best correlations (forced expiratory volume in 1 second/forced vital capacity: r=-0.55 and r=-0.58; logPC20: r=-0.46 and r=-0.45; and FeNO: r=0.42 and r=0.46, respectively). The majority of asthmatic subjects with FeNO ≥70 ppb exhibited high E/I MF levels in all lung fields (excluding the trachea) and V50%pred <80%, suggesting inflammation throughout the airway. Asthmatic subjects with FeNO <70 ppb showed high or low E/I MF levels depending on the recording position, indicating uneven airway inflammation. CONCLUSION: E/I LF and E/I MF are more useful LSA parameters for evaluating airway inflammation in bronchial asthma; 7-point lung sound recordings could be used to identify sites of local airway inflammation.