Chronic Pasteurella Multocida Bronchitis Diagnosed 3 Years After Onset of Symptoms.

We report a case of chronic infection with Pasteurella multocida in the lower respiratory tract in a man with a cat. A 77-year-old man presented with recurrent hemoptysis accompanied by bronchiectasis and an opacity in the left lung on chest computed tomography. Although the patient was seropositive for Mycobacterium avium complex, repeated sputum cultures were negative for any specific pathogen. Three years later, he was referred to our hospital for hemoptysis with enhanced opacity in the lower lobe of the left lung. Culture of bronchial lavage fluid obtained via bronchoscopy was positive for P. multocida. The patient was treated with amoxicillin-clavulanic acid for 14 days and was instructed to avoid close contact with his cat. His symptoms and chest imaging findings improved and have not recurred during more than 1 1/2 years of follow up. P. multocida can cause chronic lower respiratory infections.

High attenuation mucus in bronchi with allergic bronchopulmonary mycosis.

BACKGROUND: High-attenuation mucus (HAM) is a specific manifestation of allergic bronchopulmonary mycosis (ABPM) on chest computed tomography (CT). OBJECTIVES: To compare the diagnostic accuracy of the two definitions of HAM and to clarify the clinical and radiographic characteristics of HAM-positive and HAM-negative ABPM. METHODS: CT images at the diagnosis of ABPM using Asano's criteria were retrospectively analysed. In Study #1, radiographic data obtained using the same CT apparatus in a single institute were analysed to determine the agreement between the two definitions of HAM: a mucus plug that is visually denser than the paraspinal muscles or that with a radiodensity ≥70 Hounsfield units. In Study #2, HAM was diagnosed by comparison with the paraspinal muscles in patients with ABPM reporting to 14 medical institutes in Japan. RESULTS: In Study #1, 93 mucus plugs from 26 patients were analysed. A substantial agreement for HAM diagnosis was observed between the two methods, with a κ coefficient of 0.72. In Study #2, 60 cases of ABPM were analysed; mucus plugs were present in all cases and HAM was diagnosed in 45 (75%) cases. The median A. fumigatus-specific IgE titre was significantly lower in HAM-positive patients than in HAM-negative patients (2.5 vs. 24.3 UA /mL, p = .004). Nodular shadows were observed more frequently in the airways distal to HAM than in those distal to non-HAM mucus plugs (59% vs. 32%, p < .001). CONCLUSION: In conclusion, agreement between the two methods to diagnose HAM was substantial. HAM was associated with some immunological and radiographic characteristics, including lower levels of sensitization to A. fumigatus and the presence of distal airway lesions.

Clinical characteristics of allergic bronchopulmonary mycosis caused by Schizophyllum commune.

BACKGROUND: Allergic bronchopulmonary mycosis (ABPM) is an allergic disease caused by type I and type III hypersensitivity to environmental fungi. Schizophyllum commune, a basidiomycete fungus, is one of the most common fungi that causes non-Aspergillus ABPM. OBJECTIVE: Herein, we attempted to clarify the clinical characteristics of ABPM caused by S. commune (ABPM-Sc) compared with those of allergic bronchopulmonary aspergillosis (ABPA). METHODS: Patients with ABPM-Sc or ABPA were recruited from a nationwide survey in Japan, a multicenter cohort, and a fungal database at the Medical Mycology Research Center of Chiba University. The definition of culture-positive ABPM-Sc/ABPA is as follows: (1) fulfills five or more of the 10 diagnostic criteria for ABPM proposed by Asano et al., and (2) positive culture of S. commune/Aspergillus spp. in sputum, bronchial lavage fluid, or mucus plugs in the bronchi. RESULTS: Thirty patients with ABPM-Sc and 46 with ABPA were recruited. Patients with ABPM-Sc exhibited less severe asthma and presented with better pulmonary function than those with ABPA (p = 0.008-0.03). Central bronchiectasis was more common in ABPM-Sc than that in ABPA, whereas peripheral lung lesions, including infiltrates/ground-glass opacities or fibrotic/cystic changes, were less frequent in ABPM-Sc. Aspergillus fumigatus-specific immunoglobulin (Ig)E was negative in 10 patients (34%) with ABPM-Sc, who demonstrated a lower prevalence of asthma and levels of total serum IgE than those with ABPM-Sc positive for A. fumigatus-specific IgE or ABPA. CONCLUSIONS: Clinical characteristics of ABPM-Sc, especially those negative for A. fumigatus-specific IgE, differed from those of ABPA.

[CQ IN THE LONG-TERM MANAGEMENT OF ADULT ASTHMATIC PATIENTS WHO ARE NOT ADEQUATELY CONTROLLED WITH INHALED CORTICOSTEROIDS MONOTHERAPY, WHICH IS MORE BENEFICIAL: ADDING A LONG ACTING BETA2 AGONIST OR A LONG ACTING MUSCARINIC ANTAGONIST?]

Long-acting beta2-agonists (LABA) are preferred add-on treatment for adult asthmatic patients whose symptoms cannot be controlled with inhaled corticosteroids (ICS) alone. However, over the last decade, long-acting muscarinic antagonists (LAMA) have gained approval for use in treating asthma, and their efficacy is anticipated. Therefore, we conducted a systematic review to investigate whether the addition of LABA or LAMA is more beneficial for the long-term management of adult asthmatic patients poorly controlled on ICS monotherapy. We extracted eight relevant randomized controlled trials (represented in 18 articles) conducted by June 2022 form the corresponding Cochrane review and additional searches through medical databases (CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and ICHUSHI (https://www.jamas.or.jp/)). While the LAMA add-on group showed a significantly better improvement in some respiratory function tests, the difference between groups did not exceed the minimum clinically important difference (MCID). On the other hand, the Asthma Quality of Life Questionnaire, a quality of life metric, was significantly higher in the LABA add-on group, but the difference also did not surpass the MCID. Because no outcomes exceeded the MCID, we could not determine whether adding LABA or LAMA on ICS is more beneficial in the long-term management of adult asthmatic patients. Given that no significant differences were found in the incidence of adverse events (including serious ones), when specific adverse events associated with one treatment occur, switching to the other treatment (from LABA to LAMA, or vice versa) can be considered as an option.

Allergic bronchopulmonary aspergillosis with atopic, nonatopic, and sans asthma-Factor analysis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence or absence of asthma, either atopic or nonatopic. We have tried to explore the essential components in the pathogenesis of the disease, which are either consistent and variable according to the presence and type of asthma. METHODS: Non-cystic fibrosis ABPA cases satisfying Asano's criteria were extracted from a prospective registry of ABPA and related diseases in Japan between 2013 and 2023. According to the type of preceding asthma, ABPA was classified into three groups: ABPA sans asthma (no preceding asthma), ABPA with atopic asthma, and ABPA with nonatopic asthma. Exploratory and confirmatory factor analyses were performed to identify the components that determined the clinical characteristics of ABPA. RESULTS: Among 106 cases of ABPA, 25 patients (24%) had ABPA sans asthma, whereas 57 (54%) and 24 (23%) had ABPA with atopic and nonatopic asthma, respectively. Factor analysis identified three components: allergic, eosinophilic, and fungal. Patients with atopic asthma showed the highest scores for the allergic component (p < .001), defined by total and allergen-specific IgE titers and lung opacities, and the lowest scores for the fungal component defined by the presence of specific precipitin/IgG or positive culture for A. fumigatus. Eosinophilic components, including peripheral blood eosinophil counts and presence of mucus plugs/high attenuation mucus in the bronchi, were consistent among the three groups. CONCLUSION: The eosinophilic component of ABPA is considered as the cardinal feature of ABPA regardless of the presence of preceding asthma or atopic predisposition.

Real-world efficacy of anti-IL-5 treatment in patients with allergic bronchopulmonary aspergillosis.

Despite standard treatment with systemic corticosteroids and/or antifungal triazoles, a substantial proportion of patients with allergic bronchopulmonary aspergillosis (ABPA) experience frequent relapses and require long-term treatment despite unfavorable adverse effects. We investigated the efficacy and safety of anti-interleukin (IL)-5/IL-5 receptor α chain (Rα) monoclonal antibodies (mAbs) in patients with ABPA complicated by asthma. ABPA cases treated with anti-IL-5/IL-5Rα mAbs were collected from 132 medical institutes in 2018 and published case reports in Japan. Clinical outcomes, laboratory and physiological data, and radiographic findings during 32 weeks before and after treatment were retrospectively evaluated. We analyzed 29 cases of ABPA: 20 treated with mepolizumab and nine with benralizumab. Treatment with anti-IL-5/IL-5Rα mAbs reduced the frequency of exacerbations (p = 0.03), decreased the dose of oral corticosteroids (p < 0.01), and improved pulmonary function (p = 0.01). Mucus plugs in the bronchi shrank or diminished in 18 patients (82%). Despite the clinical/radiographical improvement, serum levels of total IgE, the key biomarker for the pharmacological response in ABPA, were unchanged. Anti-IL-5/IL-5Rα mAbs that directly target eosinophils are promising candidates for the treatment of patients with ABPA, especially those with mucus plugs in the bronchi.

Moldy odor from air conditioners in the residences of Japanese participants with and without asthma.

Fungi, a major allergen associated with asthma onset and severity, can contaminate air conditioners if not properly maintained. We surveyed the prevalence and risk factors associated with fungal contamination of air conditioners and patient behavior to reduce this contamination. Japanese adults aged ≥30 years registered in the database of an Internet research company were asked to participate in an online survey. A moldy odor from the air conditioners in their residences was used as an indicator of fungal contamination. Among a total of 1006 adults, including 631 patients with asthma, 37.1% reported a moldy odor from air conditioners. The prevalence was higher in residences with indoor condensation and in air conditioners used for ≥6 years or frequently during the summer, but was lower in air conditioners with an auto-cleaning function. The risk of indoor condensation was higher in apartments, in the presence of an aquarium, and in the absence of a 24-h ventilation system. These risk factors did not differ between the residences or air conditioners of participants with and without asthma. Asthmatic patients were conscious of indoor air quality; however, do not necessarily take appropriate measures to reduce indoor mold contamination, possibly due to a lack of knowledge. In conclusion, appropriate patient education is required to reduce environmental fungal contamination and improve asthma control.

Prognosis of acute exacerbation in idiopathic pulmonary fibrosis with pulmonary emphysema: a retrospective cohort study in Japan.

OBJECTIVES: To analyse the clinical characteristics and prognosis of acute exacerbation (AE) in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary emphysema. DESIGN: A multicentre retrospective cohort study SETTING: Two university hospitals in Japan PARTICIPANTS: Patients admitted to hospitals due to AE of IPF diagnosed based on a multidisciplinary discussion. INTERVENTIONS: None PRIMARY AND SECONDARY OUTCOME MEASURES: 90-day mortality rate METHODS: We retrospectively analysed consecutive patients with AE of IPF, with or without pulmonary emphysema, admitted to two university hospitals between 2007 and 2018. RESULTS: Among 62 patients (median age, 75 years; 48 men) admitted for AE of IPF, 29 patients (46%) presented with concomitant pulmonary emphysema. There was no significant difference in the arterial partial oxygen pressure/fraction of inhaled oxygen (P/F) ratio or other laboratory and radiographic data between patients with and without emphysema. The 90-day mortality rate was significantly lower in patients with emphysema than in those with IPF alone (23% vs 52%, p=0.03). The median survival time was significantly longer in patients with emphysema than in those with IPF alone (405 vs 242 days, p=0.02). CONCLUSION: Patients with IPF and emphysema had better short-term survival after AE than those with non-emphysematous IPF.

Efficacy of Prophylactic Antibiotic Use in Preventing Post-bronchoscopy Pneumonia in Lung Cancer Patients.

OBJECTIVE: Post-bronchoscopy pneumonia can affect the prognosis of lung cancer patients. This prospective study examined the efficacy of prophylactic antibiotics for lung cancer patients at high-risk of post-bronchoscopy pneumonia, determined by our prediction score, using three risk factors: age 70 years or older, current smoking, and central tumors visualized on CT. METHODS: Patients with lung cancer who underwent diagnostic bronchoscopy between June 2018 and March 2020 with a score of 2 points or higher were enrolled. Sulbactam/ampicillin was administered intravenously within one hour prior to bronchoscopy, followed by oral clavulanate/amoxicillin for three days. We used the data of lung cancer patients who underwent diagnostic bronchoscopy between April 2012 and July 2014 and exhibited a score of 2 or higher as the historical control. RESULTS: Post-bronchoscopy pneumonia occurred in none of the 24 patients in the prophylaxis group and in 17 of 144 patients in the control group, with no significant difference in the incidence of pneumonia between the two groups. CONCLUSIONS: Antibiotic prophylaxis can be effective and safe for the patients high-risk of post-bronchoscopy pneumonia. A multicenter prospective study to examine the effects of prophylactic antibiotics in high-risk patients is feasible with a modest number of participants.

COVID-19 vaccine-associated organizing pneumonia.

We report the first case of organizing pneumonia (OP) associated with a new coronavirus disease (COVID-19) vaccination. A 78-year-old woman developed cough and dyspnoea 10 days after receiving BNT162b2. Chest computed tomography (CT) revealed consolidation in the bilateral lower lobes of the lungs. Although antibiotic treatment did not improve her symptoms, she received a second vaccination as scheduled. She was referred to our hospital because of worsening dyspnoea on day 9 after the second vaccination, with reversed halo signs in the bilateral lower pulmonary lobes and new consolidation in the left lingual region on chest CT on day 15. She was diagnosed with OP based on bronchoalveolar lavage and transbronchial lung biopsy findings. Treatment with oral prednisolone 0.5 mg/kg/day immediately improved the symptoms and chest imaging findings. In the absence of other triggering factors, we considered this case as being COVID-19 vaccine-associated following the first and second vaccinations.

Trans-arterial Embolization in a Patient with Unilateral Absence of Pulmonary Artery: Treatment Success and the Four-year Prognosis.

Unilateral absence of the pulmonary artery (UAPA) with or without other anomalies in the heart is a rare congenital malformation. A 55-year-old Filipino woman without a remarkable medical history was admitted to our hospital for hemoptysis. Contrast-enhanced chest computed tomography revealed the absence of the left pulmonary artery. Echocardiography and right heart catheterization showed no cardiac malformations or pulmonary hypertension. We diagnosed her with isolated left-sided UAPA and performed transarterial embolization of the left inferior phrenic artery. This resolved the hemoptysis, and there was no recurrence during the four-year follow-up period.

Rhabdomyolysis Caused by Gefitinib Overdose.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are common therapeutic agents for EGFR mutation-positive advanced non-small-cell lung cancer. There has been no report of rhabdomyolysis caused by an overdose of EGFR-TKIs. We herein review the existing literature on the subject and report a rare case of rhabdomyolysis due to an overdose of gefitinib, an EGFR-TKI.

Diagnosis of pleural empyema/parapneumonic effusion by next-generation sequencing.

BACKGROUND: Although a microbiological diagnosis of pleural infection is clinically important, it is often complicated by prior antibiotic treatment and/or difficulties with culturing some bacterial species. Therefore, we aimed to identify probable causative bacteria in pleural empyema/parapneumonic effusions by combining 16S ribosomal RNA (rRNA) gene amplification and next-generation sequencing (NGS). METHODS: Pleural fluids were collected from 19 patients with infectious effusions and nine patients with non-infectious malignant effusions. We analysed DNA extracted from the pleural fluid supernatant by NGS using the Genome Search Toolkit and GenomeSync database, either directly or after PCR amplification of the 16S rRNA gene. Infectious and non-infectious effusions were distinguished by semi-quantitative PCR of the 16S rRNA gene. RESULTS: Only 8 (42%) effusions were culture-positive, however, NGS of the 16S rRNA gene amplicon identified 14 anaerobes and 7 aerobes/facultative anaerobes in all patients, including Streptococcus sp. (n = 6), Fusobacterium sp. (n = 5), Porphyromonas sp. (n = 5), and Prevotella sp. (n = 4), accounting for >10% of the total genomes. The culture and NGS results were discordant for 3 out of 8 patients, all of whom had previously been treated with antibiotics. Total (2ΔCT value in semi-quantitative PCR of the 16S rRNA gene) and specific (total bacterial load multiplied by the proportion of primary bacteria in NGS) bacterial loads could efficiently distinguish empyema/parapneumonic effusion from non-infectious effusion. CONCLUSION: Combining NGS with semi-quantitative PCR can facilitate the diagnosis of pleural empyema/parapneumonic effusion and its causal bacteria.

Transudative Pleural Effusion Associated with Extramedullary Hematopoiesis.

The authors report a case of transudative pleural effusion associated with extramedullary hematopoiesis due to the presence of a myeloproliferative neoplasm, which was unclassified. A 71-year-old man presented with right pleural effusion during an exacerbation of thrombocytosis. The pleural effusion was transudative, although there was no history of cardiac failure or hypoalbuminemia, and treatment with diuretics failed. Extramedullary hematopoiesis was diagnosed in bilateral paravertebral soft tissue and the liver on 111In bone marrow scintigraphy. The administration of hydroxyurea simultaneously reduced peripheral blood platelet count and pleural effusion within 2 weeks. The possible cause of transudative pleural effusion in association with extramedullary hematopoiesis is discussed.

Cytokine/Chemokine/Growth Factor Levels in Malignant Pleural Effusion of Non-small Cell Lung Cancer.

OBJECTIVE: Malignant pleural effusions (MPEs) deteriorate the quality of life in patients with advanced stages of cancer. Although vascular endothelial growth factor (VEGF) is known to be a key factor for MPE formation, it is not fully clarified whether there are other components related to its appearance. METHODS: Pleural effusion and serum samples were collected from patients with MPEs of non-small cell lung cancer. Cellular analysis of pleural effusion was performed using fluorescence flow cytometry. The concentrations of 12 cytokines, chemokines, and growth factors in MPEs and serum samples were analyzed using the cytometric bead array method. RESULTS: Fifteen patients (median age: 70 years, 11 males) with non-small cell lung cancer (13 adenocarcinoma, 2 squamous cell carcinoma) were enrolled in this study. Concentrations of VEGF, interleukin (IL)-5, IL-6, IL-8, IL-12/IL-23p40, and C-C motif chemokine ligand (CCL) 2 were significantly higher in MPE than in serum. Pleural IL-5 levels correlated with malignant cell numbers in MPE. There was no factor related to the total amount of drained effusion or period of chest tube insertion. CONCLUSIONS: Production of six molecules were increased in the pleural cavity with MPE of non-small cell lung cancer. Complex interactions among these molecules may regulate MPE formation.

Successful Treatment of a Patient with Lung Adenocarcinoma Harboring Compound EGFR Gene Mutations, G719X and S768I, with Afatinib.

Mutations in the gene encoding epidermal growth factor receptor (EGFR) are the most frequent driver mutations in lung adenocarcinoma in Japan. Exon 19 deletion and L858R mutation in exon 21 are the most common EGFR mutations. Uncommon mutations, such as G719X, S768I, and L861Q, and compound mutations, combinations of 2 common or uncommon mutations, have also been reported. EGFR tyrosine kinase inhibitors (TKIs) are effective against cancers harboring common mutations; however, their efficacy against cancers with uncommon or compound mutations remains unclear. We report the case of a 67-year-old man with lung adenocarcinoma (clinical stage IIIA [cT1N2M0]), harboring an uncommon compound mutation, G719X and S768I. The cancer progressed within 2 months of initial chemoradiotherapy. Treatment with afatinib (40 mg/day) produced a partial response, which was maintained for 17 months with continued treatment. A literature review revealed that lung cancer with G719X/S768I compound mutation exhibited good response to EGFR-TKIs, even better than that of lung cancers with single uncommon mutations.

Effectiveness and Safety of Omalizumab in Patients with Allergic Bronchopulmonary Aspergillosis Complicated by Chronic Bacterial Infection in the Airways.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence of predisposing conditions such as asthma and cystic fibrosis. Even ABPA accompanied by asthma is often complicated by chronic Pseudomonas aeruginosa or nontuberculous mycobacterial infection of the lower respiratory tract, rendering treatment with corticosteroids difficult. There have been several reports on the effectiveness of omalizumab, an anti-IgE antibody, in patients with ABPA. We analyzed the effectiveness and adverse effects of omalizumab in ABPA patients with chronic respiratory infections. METHODS: Using our nationwide survey database and published case reports, we identified patients with severe asthma and ABPA who fulfilled the International Society for Human and Animal Mycology criteria and who had been treated with omalizumab. Exacerbation rates, control of symptoms, doses of oral corticosteroids, and pulmonary function were evaluated. RESULTS: Among 25 patients with ABPA treated with omalizumab (median age 62 years, range 33-83 years), 12 patients had a chronic bacterial infection of the lower airways attributable to P. aeruginosa (n = 6) or nontuberculous mycobacteria (n = 6) at the initiation of omaliz-umab. Treatment with omalizumab reduced the frequency of exacerbations and systemic corticosteroid doses and improved pulmonary function. There were no significant adverse events or worsening of infection during treatment with omalizumab, except for injection-site reactions. CONCLUSIONS: Treatment with omalizumab was effective and safe in patients with ABPA, regardless of comorbid chronic respiratory tract infections.