Respiratory investigation最新文献

Background

Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs.

Methods

We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses.

Results

The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021).

Conclusion

Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection.

α₁-antitrypsin deficiency (AATD) is a hereditary disorder with a global prevalence that differs across regions. AATD is highly prevalent in Europe and North America but rarely found in Asian countries, including Japan, possibly because of the founder effect of the pathogenic SERPINA1 variants PI*Z and PI*S. However, AATD remains underdiagnosed even in high-prevalence and low-prevalence regions, possibly because of lack of awareness. In this study, we surveyed open Japanese genetic variation databases to estimate AATD prevalence in Japan. We identified allelic frequencies (AFs) of 5 among the 14 major pathogenic SERPINA1 variants from three datasets, collectively derived from 63,119 Japanese participants. The mean AF was determined to be 8.56 × 10⁻⁴ (95% confidence interval [CI]: 6.43 × 10⁻⁴ to 1.12 × 10⁻³). Given that this represents the entire Japanese population, one AATD patient was speculated to be born per 1.37 × 10⁶ births (95% CI: 7.97 × 10⁵ to 2.42 × 10⁶) in Japan. Our results support the prevailing notion that AATD is extremely rare in Japan.

Background

The diagnosis of fibrotic hypersensitivity pneumonitis (fHP) from other interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF), is often difficult. This study aimed to examine computed tomography (CT) findings that were useful for differentiating between fHP and IPF and to develop and validate a radiological diagnostic model.

Methods

In this study, 246 patients (fHP, n = 104; IPF, n = 142) from two institutions were included and randomly divided into the test (n = 164) and validation (n = 82) groups (at a 2:1 ratio). Three radiologists evaluated CT findings, such as pulmonary fibrosis, small airway disease, and predominant distribution, and compared them between fHP and IPF using binomial logistic regression and multivariate analysis. A prognostic model was developed from the test group and validated with the validation group.

Results

Ground-glass opacity (GGO) with traction bronchiectasis (TB), honeycombing, hypoattenuation area, three-density pattern, diffuse craniocaudal distribution, peribronchovascular opacities in the upper lung, and random distribution were more common in fHP than in IPF. In multivariate analysis, GGO with TB, peribronchovascular opacities in the upper lung, and random distribution were significant features. The area under the curve of the fHP diagnostic model with the three aforementioned CT features was 0.733 (95% confidence interval [CI], 0.655–0.811, p < 0.001) in the test group and 0.630 (95% CI, 0.504–0.755, p < 0.047) in the validation group.

Conclusion

GGO with TB, peribronchovascular opacities in the upper lung, and random distribution were important CT features for differentiating fHP from IPF.

Idiopathic pulmonary fibrosis (IPF) is the archetypal interstitial lung disease. It is a chronic progressive condition that is challenging to manage as the clinical course of the disease is often difficult to predict. The prevalence of IPF is rising globally and in Japan, where it is estimated to affect 27 individuals per 100,000 of the population. Greater patient numbers and the poor prognosis associated with IPF diagnosis mean that there is a growing need for disease management approaches that can slow or even reverse disease progression and improve survival. Considerable progress has been made in recent years, with the approval of two antifibrotic therapies for IPF (pirfenidone and nintedanib), the availability of Japanese treatment guidelines, and the creation of global and Japanese disease registries. Despite this, significant unmet needs remain with respect to the diagnosis, treatment, and management of this complex disease. Each of these challenges will be discussed in this review, including making a timely and differential diagnosis of IPF, uptake and adherence to antifibrotic therapy, patient access to pulmonary rehabilitation, lung transplantation and palliative care, and optimal strategies for monitoring and staging disease progression, with a particular focus on the status in Japan. In addition, the review will reflect upon how ongoing research, clinical trials of novel therapies, and technologic advancements (including artificial intelligence, biomarkers, and genomic classification) may help address these challenges in the future.

Background

Severe respiratory failure requires numerous interventions and its clinical implementation changes over time. We aimed to clarify the clinical practice and prognosis of severe respiratory failure and its changes over time.

Methods

In a nationwide Japanese administrative database from 2016 to 2019, we identified nonoperative patients with severe respiratory failure without congestive heart failure as the main diagnosis who received mechanical ventilation (MV) for more than four days. We examined trends in patient characteristics, adjunctive interventions, and prognosis.

Results

Among 66,905 patients included in this study, patients received antibiotics (90%), high-dose corticosteroids (14%), low-dose corticosteroids (18%), and 51% were admitted to the critical care unit. Hospital mortality was 35%. Median mechanical ventilation lasted 10 days. Tracheostomy occurred in 23% of cases. Median critical care and hospital stays were 10 and 25 days, respectively. Among survivors, 23% had mechanical ventilation dependency at hospital discharge. Large relative changes in adjunctive therapies included fentanyl (30%–38%), rocuronium (4.4%–6.7%), vasopressin (3.8%–6.0%), early rehabilitation (27%–38%), extracorporeal membrane oxygenation (0.7%–1.2%), dopamine (15%–10%), and sivelestat (8.6%–3.5%). No notable changes were seen in mechanical ventilation duration, tracheostomy, critical care unit stay, hospital stay, or ventilator dependency at discharge, except for a slight reduction in hospital mortality (36%–34%).

Conclusions

Several adjunctive therapies for severe respiratory failure changed from 2016 to 2019, with an increase in evidence-based practices and a slight decrease in hospital mortality.

Background

The diagnostic criteria for respiratory sarcopenia have been recently reported. However, no studies have clarified the characteristics of skeletal muscle impairment of the limbs in subjects with respiratory sarcopenia. This study aimed to explore the factors, including skeletal muscle, associated with probable respiratory sarcopenia in elderly subjects.

Methods

Subjects were classified into the probable respiratory sarcopenia group and nonrespiratory sarcopenia group. Probable respiratory sarcopenia was defined as the concurrent presence of respiratory muscle weakness (as less than the predicted value calculated from age, sex, and height) and low skeletal muscle mass (<7.0 kg/m² in males and 5.7 kg/m² in females). The following factors were measured: respiratory muscle strength, skeletal muscle mass index, muscle thickness and echo intensity of the rectus femoris, extracellular-to-intracellular water ratio, hand grip strength, 5 sit-to-stand, knee extension strength, bone mineral density, age, sex, body mass index, degree of frailty, presence or absence of medical history, presence or absence of habitual exercise, period of time since the start of exercise, and number of hours of exercise at a time. The association subjects with probable respiratory sarcopenia were analyzed using hierarchical logistic regression analysis.

Results

Twenty-six with probable respiratory sarcopenia and 54 with nonrespiratory sarcopenia were included. Hierarchical logistic regression analysis revealed that echo intensity was a significant predictor of probable respiratory sarcopenia. The odds ratio for echo intensity was 2.54 (95% confidence interval: 1.04–6.23).

Conclusions

Our results suggest that a decrease in muscle quality in the lower extremity is associated with probable respiratory sarcopenia.

Background

Some case reports have found that corticosteroid treatments shrunk thymoma lesions remarkably after the failure of chemotherapy or surgery. However, few studies have comprehensibly evaluated the antitumor effects of corticosteroids in patients with invasive thymomas.

Methods

We reviewed the medical records of 13 consecutively enrolled patients with locally advanced or metastatic thymomas treated via corticosteroid monotherapies from January 2010 to March 2021 in our institute. A Cox's proportional hazard model and the Kaplan-Meier method were used to identify factors associated with survival.

Results

The median follow-up time was 26 months (range, 13–115 months). The median initial dose of corticosteroid was 0.90 mg/kg/day prednisolone equivalent (range, 0.4–1.1 mg/kg/day). Of the 13 cases, 7 (53.8%, 95% CI: 0.25–0.81) exhibited a partial response and 5 (38.5%, 95% CI: 0.14–0.68) stable disease. The median progression-free survival was 5.7 months [95% confidence interval (CI): 1.5–9.6 months]. The median overall survival was 25.3 months (95% CI: 7.1–not attained). The median duration of corticosteroid use was 3 months (range, 1–64 months). Patients with WHO subtype B thymomas exhibited a better overall response rate to corticosteroids than did patients with other disease subtypes (75%, 95% CI: 0.19–0.99). Adverse events of Grade 3 or more were not observed.

Conclusions

Corticosteroids are clinically valuable for patients with thymomas.

A 50-year-old man was diagnosed with hypersensitivity pneumonitis caused by the environment of his bar owing to worsening symptoms, laboratory test results, and computed tomography images after an environmental inhalation challenge test. His hypersensitivity pneumonitis exacerbated despite receiving prednisolone 20 mg/day. The patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched unrelated donor for myelodysplastic syndrome. No exacerbation of hypersensitivity pneumonitis was observed after HSCT. An environmental inhalation challenge test involving exposure to his bar confirmed the remission of hypersensitivity pneumonitis after HSCT. This case demonstrates that hypersensitivity pneumonitis can be remitted by HSCT.

The success rate of omalizumab discontinuation is 50–75.5%. However, such data are scarce in Japan. We retrospectively investigated the clinical progression following the cessation of long-term omalizumab treatment (>5 years) in severe allergic asthma patients who have achieved super-responder status, defined as being off any oral maintenance corticosteroids without experiencing exacerbations requiring systemic corticosteroids for >1 year. Six (28.6%) among 21 patients recommenced after a median period of 5.5 (4.3–12.5) months later due to exacerbated asthma control, resulting in improved asthma management for all patients. The rates of patients who successfully remained off omalizumab treatment for 1 and 2 years were 72.4% and 65.8%, respectively. Specific IgE levels after discontinuing omalizumab treatment significantly decreased compared to those at initiating this treatment in 10 patients who successfully remained off this treatment. Therefore, discontinuing omalizumab treatment may be considered for patients continuing treatment beyond 5 years and achieving super-responder status.

Gastroesophageal reflux disease (GERD) is one of the most common comorbidities of chronic obstructive pulmonary disease (COPD). Decreased lower and upper esophageal sphincter pressures, esophageal dysmotility, high transdiaphragmatic pressure, and decreased saliva secretion have been implicated as mechanisms leading to the development of GERD in COPD. Clinically, comorbid GERD in COPD is reportedly associated with worse symptoms, quality of life, and lung function, as well as a high risk of exacerbations. Aspiration of regurgitation and the cholinergic-mediated esophagobronchial reflex play a significant role in the pathophysiology. Abnormal swallowing reflexes and discoordination of swallowing can worsen aspiration. The diagnosis of GERD is not based on a single criterion; however, various approaches, including questionnaires and endoscopic evaluations, can be widely applied in clinical settings. Due to the increased risk of esophageal and gastric cancers in patients with COPD, the threshold for endoscopic examination should be low. Acid inhibitory agents, such as proton pump inhibitors and histamine H2 receptor antagonists, and prokinetic agents, including mosapride and itopride, are clinically used to treat GERD. Endoscopic fundoplication can be performed in patients with GERD refractory to medical treatment. There is still insufficient evidence, but an increasing number of studies have suggested the clinical efficacy of treatment in patients with COPD and GERD. As GERD is an evaluative and treatable common disease, and access to evaluation and treatment is relatively easy, clinicians should provide adequate care for GERD in the management of COPD.