Effectiveness of upfront triple oral combination therapy with additional pirfenidone in a patient with severe pulmonary hypertension associated with lung diseases.

Diagnosis and treatment of pulmonary hypertension (PH) in patients with lung diseases (PH-LD) remain unestablished and pose significant challenges. In this report, we present a case of a 77-year-old patient with an indeterminate for usual interstitial pneumonia pattern along with chronic obstructive pulmonary disease, who developed groups 1 and 3 PH. Following diagnosis, upfront triple oral combination therapy (UTOCT) with macitentan, sildenafil, and selexipag was initiated. Stability in disease progression was achieved over 4 years with the addition of pirfenidone to address interstitial lung disease progression. To the best of our knowledge, this represents the first reported case of PH-LD, where disease control was maintained with the addition of pirfenidone to UTOCT. This case suggests that some patients with PH-LD, presenting with groups 1 and 3 PH, may benefit from combined UTOCT and antifibrotic agents, potentially improving symptoms and extending their prognosis.

Successful excision of an inflammatory endobronchial polyp using biopsy forceps with improvement in FEV1 in a patient with allergic bronchopulmonary aspergillosis: A case report.

Inflammatory endobronchial polyps (IEPs) are rare, benign bronchial tumors posing diagnostic and therapeutic challenges owing to limited data. A 55-year-old man, receiving treatment for allergic bronchopulmonary aspergillosis, presented with a one-week history of fever and purulent sputum. Diagnosed with pneumonia, he received antimicrobial treatment. However, because of persistent symptoms, an endobronchial tumor was suspected on computed tomography. IEP was confirmed through flexible bronchoscopy with forceps biopsy, and polyp removal improved symptoms, lung function, and imaging.

Pretreatment asthma control test score as a predictive score for clinical remission after bronchial thermoplasty in younger patients with severe asthma and preserved lung function.

OBJECTIVE: Bronchial thermoplasty (BT) decreases the incidence of asthma exacerbations, emergency room visits, and hospitalizations among patients with severe asthma. Predictors of BT effectiveness remain unclear as its mechanism of action and invasiveness remain obscure. This study aimed to identify factors that could predict BT outcomes. METHODS: Two respiratory physicians treated 20 consecutive patients with severe asthma using BT. The patients were assigned to groups based on clinical remission following an expert consensus proposed in 2020. Predictors of clinical remission were analyzed using asthma control test (ACT) score, pulmonary function and blood tests, and fractional exhaled nitric oxide. RESULTS: At baseline, the median age was 44 years (interquartile range [IQR], 31.0-52.8), and pre-bronchodilator (pre-BD) percent predicted forced expiratory volume in one second (%FEV1) was 85.9% (IQR, 74.8-100.5). Six (30%) patients achieved clinical remission. Among the patients treated with biologics, 20% had clinical remission, and 20% discontinued biologic therapy. The pre-BT ACT score was significantly lower in the group with than without remission (11.0 [IQR, 8.0-14.5] vs. 15.0 [IQR, 11.0-17.3], p = .016). Adverse events did not significantly differ between the groups. CONCLUSIONS: To the best of our knowledge, this is the first study to use clinical remission as a criterion for evaluating BT efficacy. The pre-BT ACT score might a the predict response to BT in younger adult patients with severe asthma and pre-BD %FEV1 ≥ 70%.

Safety of Readministration of EGFR-TKI After Onset of Interstitial Lung Disease in Advanced EGFR-Mutated NSCLC: A Systematic Review and Meta-Analysis.

BACKGROUND: In patients with epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitor (TKI) interruption due to EGFR-TKI-induced interstitial lung disease (ILD) is a factor for shorter overall survival (OS). Several retrospective cohort studies have reported an OS-prolonging effect of the readministration of EGFR-TKIs. This study aimed to determine the safety of readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. METHODS: The PubMed, CINAHL, and Web of Science databases were systematically searched until May 30, 2023. The primary outcome was successful readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. RESULTS: A total of 690 patients were included in this meta-analysis. The initial EGFR-TKI-induced ILD rate was 13.6% (95% confidence interval [CI]:6.4-20.9). Readministration rate of EGFR-TKI after onset of EGFR-TKI-induced ILD was 40.2% (95% CI: 26.7-53.7). The successful readministration rate of EGFR-TKIs after onset of EGFR-TKI-induced ILD was 81.9% (95% CI: 73.8-90.0). Successful rate of EGFR-TKI readministration in patients with Grade 2 or higher adverse events post initial EGFR-TKI therapy was 76.1% (95% CI: 55.6-96.6). CONCLUSIONS: Although initial EGFR-TKI-induced ILD has a relatively high incidence, EGFR-TKI readministration after the onset of EGFR-TKI-induced ILD may be a viable treatment option.

Retrospective analysis of independent predictors of progression-free survival in patients with EGFR mutation-positive advanced non-small cell lung cancer receiving first-line osimertinib.

BACKGROUND: Clinically measurable factors affecting the progression-free survival (PFS) of patients receiving osimertinib as first-line therapy for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC) have not yet been established. METHODS: We retrospectively reviewed the medical records of 61 patients treated with osimertinib as primary therapy for EGFR mutation-positive advanced NSCLC at Yokohama City University Medical Center between August 2018 and March 2022. Our objective was to identify the independent predictors of PFS. RESULTS: The median age of participants was 74 years. Overall, 73.8% had good (0-1) Eastern Cooperative Oncology Group performance status (PS), and 98.4% had histology of adenocarcinoma. The EGFR mutation was exon19 deletion in 52.5% and exon21 L858R in 44.3% of patients. Programmed death-ligand 1 tumor proportion score >50% was observed in 21.3% and liver metastasis in 9.9% of patients. Median PFS was 19.5 months (95% confidence interval [CI]: 10.6-31.6), and overall survival was not reached. The objective response rate was 68.9%, and disease control rate was 93.4%. Multivariate analysis showed that poor PS (2-4) negatively impacted PFS (hazard ratio, 3.79; 95% CI: 1.46-9.87; p = 0.006). Median PFS in the good PS and poor PS groups was 20.4 months (95% CI: 12.4-not evaluable) and 7.2 months (95% CI: 7.2-19.5), respectively. Interstitial lung disease of all grades and grade 3 was observed as an adverse event in 6.6 and 4.9% of patients, respectively. CONCLUSION: Poor PS was associated with poor prognosis in patients with EGFR mutation-positive advanced NSCLC treated with osimertinib as first-line therapy.

Combination of Pembrolizumab With Platinum-containing Chemotherapy for Pulmonary Enteric Adenocarcinoma.

Background/Aim: Pulmonary enteric adeno-carcinoma (PEAC) is a rare type of non-small cell lung cancer (NSCLC), for which no established standard treatment exists. Combination therapy with the anti-programmed cell death protein 1 antibody pembrolizumab and platinum-containing chemotherapy is the standard treatment for NSCLC patients, but its effectiveness in PEAC is uncertain. Case Report: We present a 68-year-old man with chemotherapy-naïve advanced PEAC who responded to a combination of pembrolizumab and platinum-containing chemotherapy. Conclusion: The number of PEAC cases is small, and no clinical trials have been conducted to determine an optimal chemotherapy regimen. In this case, we showed that pembrolizumab combined with platinum-containing chemotherapy might effectively treat PEAC.

Real-Time PCR Assay for the Diagnosis and Quantification of Co-infections by Diaporthe batatas and Diaporthe destruens in Sweet Potato.

Foot rot disease caused by Diaporthe destruens (formerly Plenodomus destruens) has become a major concern for the production of sweet potato [Ipomoea batatas (L.) Lam.] in Japan. A related fungus Diaporthe batatas, which causes dry rot disease of sweet potato, is native and is widespread in fields in Japan. The similar characteristics of these two pathogens pose a challenge for conventional disease diagnosis. Currently, there are no effective molecular measures for identifying and distinguishing D. destruens and D. batatas. Here, we demonstrate a real-time PCR assay that distinguishes and quantifies D. batatas and D. destruens from co-infected sweet potato. The assay was performed with various simulated DNA combinations of D. batatas and D. destruens ranging from 1:1 to 1:100000. The assay was also used with the ratios of D. batatas: D. destruens: sweet potato DNA ranging from 1:1:1 to 1:1:100000. These assays produced a specific amplification product for each of the pathogens, and quantified the fungal biomass over the entire range tested without detecting false positives. The assay was validated by using infected sweet potato collected from various fields; it showed sufficient sensitivity and specificity to quantify and distinguish D. batatas and D. destruens from these field samples. Thus, our real-time PCR assay would be a useful tool for diagnosis of D. batatas and D. destruens and is expected to provide the foundation for the design of integrated disease management strategies for foot rot disease in sweet potato.

Nivolumab-induced Vogt-Koyanagi-Harada-like Syndrome and Adrenocortical Insufficiency with Long-term Survival in a Patient with Non-small-cell Lung Cancer.

A 58-year-old man was diagnosed with lung adenocarcinoma with a tumor proportion score of 10%. After six cycles of second-line chemotherapy with nivolumab, he achieved a complete response (CR) but developed uveitis and sensorineural hearing disorder, which were consistent with Vogt-Koyanagi-Harada (VKH)-like syndrome. Simultaneously, pituitary adrenocortical insufficiency was identified. Nivolumab discontinuation and systemic corticosteroid administration resolved these immune-related adverse events (irAEs). The patient has maintained a CR without any chemotherapy for approximately two years. We herein report a patient with a long-term progression-free survival despite chemotherapy discontinuation due to irAEs, including VKH-like syndrome, which were appropriately managed.

Real-Time PCR Detection of the Onion Downy Mildew Pathogen Peronospora destructor From Symptomless Onion Seedlings and Soils.

An outbreak of downy mildew disease of onion, caused by Peronospora destructor, in Japan in 2016 necessitated a reevaluation of the primary inoculum sources to optimize disease management. Detection of the P. destructor pathogen in plants with asymptomatic infection and in soil would guide the application of fungicides according to the extent of infection before disease development. Here, we detected P. destructor in both plants and soil using newly developed primer sets (Pd ITS and Pd ITS 614) by both conventional and real-time PCR. Validation by real-time PCR with Pd ITS 614 showed that P. destructor DNA was amplified from symptomless seedlings at 3.7 × 102 to 1.0 × 100 conidium cells/50 mg leaf tissue, suggesting the detection of asymptomatic infection. Real-time PCR with Pd ITS amplified pathogen DNA from field soils at 1.6 × 103 to 8.3 × 101 oospore cells/g of soil. This real-time PCR assay provides a useful tool for identifying and quantifying inoculum sources, which may be the foundation of the design of integrated disease management strategies.

Acute and Subacute Oral Toxicity of Deoxynivalenol Exposure in a Dermatophagoides farinae-Induced Murine Asthma Model.

Previously, researchers have demonstrated that mycotoxin deoxynivalenol (DON) significantly enhances immunocyte activation. However, the interaction between DON exposure and immune disorders remains unclear. In this study, we aimed to investigate whether acute and subacute oral exposure to DON exacerbates the development of respiratory allergy using a mite allergen (Dermatophagoides farina, Derf)-induced mouse model of asthma. The direct relationship between DON exposure and asthma development was examined following acute oral DON administration (0, 0.1, or 0.3 mg/kg body weight), immediately before the final mite allergen challenge. Simultaneously, the influence of subacute oral exposure via low dose DON contaminated wheat (0.33 ppm) was evaluated using the same settings. To detect the proinflammatory effects of DON exposure, we examined the total and Derf-specific serum IgE levels, histology, number of immunocytes, and cytokine and chemokine secretion. Acute oral DON significantly enhanced the inflammatory responses, including cellular infiltration into bronchoalveolar lavage fluid, infiltration of immunocytes and cytokine production in local lymph nodes, and cytokine levels in lung tissues. Corresponding proinflammatory responses were observed in a mouse group exposed to subacute oral DON. In vivo results were validated by in vitro experiments using the human bronchial epithelial (BEAS-2B) and human eosinophilic leukemia (EOL-1) cell lines. Following exposure to DON, the secretion of interleukin (IL)-1ß, IL-6, IL-8, and/or tumor necrosis factor-α in BEAS-2B cells, as well as EoL-1 cells, increased significantly. Our findings indicate that DON exposure is significantly involved in the proinflammatory response observed in respiratory allergy.