A Case of Overlap of Chronic Pulmonary Aspergillosis on Allergic Bronchopulmonary Aspergillosis.

An 80-year-old woman who developed allergic bronchopulmonary aspergillosis (ABPA) was admitted to our institution in 2023 for an enlarged pulmonary mass lesion. She had developed ABPA in 2017, and corticosteroid therapy had improved the mucoid impaction of the bronchi. Because part of the lesion remained, increased doses of corticosteroid, antifungals, and biologics were administered, but the pulmonary lesion enlarged in 2022. Bronchoscopy showed necrotic tissue in the bronchial lumen, and bronchial washing fluid showed neutrophilic inflammation and fungal hyphae. We subsequently diagnosed her as having chronic pulmonary aspergillosis overlapping ABPA, and voriconazole was started that resulted in shrinkage of the nodules.

Drug-induced lung disease due to topical minoxidil.

A 55-year-old man presented to our institution with abnormal chest X-ray shadows. Chest computed tomography (CT) showed left-sided interlobular septal thickening; thus, we suspected lymphangitis carcinomatosis and other disorders that show similar CT findings. Bronchoscopy and laboratory and imaging studies yielded no diagnostic findings. Pulmonary shadows during follow-up spontaneously improved then worsened. Thoracoscopic lung biopsy samples showed interstitial pneumonia and granulomas but the etiology of the pulmonary lesion could not be determined. At seven years after presentation, the patient's pulmonary shadows had gradually deteriorated, and he reported using topical minoxidil. His history of minoxidil use was linked to changes in the pulmonary shadows. The diagnostic delay was due to the patient's hesitancy to report drugs obtained online and the difficulty in obtaining such a history.

Utility of budgerigar/pigeon/parrot-specific IgG antibody with ImmunoCAP® in bird-related hypersensitivity pneumonitis caused by other bird species and duvet.

BACKGROUND: Bird-related hypersensitivity pneumonitis (BRHP) is an extrinsic allergic alveolitis caused by inhalation of bird antigens. Although the measurement of serum-specific IgG antibodies against budgerigar, pigeon, and parrot with ImmunoCAP® is available in Japan, the utility of the test for patients with causes by bird breeding other than these three species, including contact with wild birds/poultry/bird manure, and use of a duvet is unknown. METHODS: Of the 75 BRHP patients who participated in our previous study, 30 were included. Six cases were caused by bird breeding of species other than pigeon, budgerigar, and parrot, seven were in contact with wild birds/poultry/bird manure, and 17 were using a duvet. Bird-specific IgG antibodies were compared among the patients, 64 controls, and 147 healthy participants. RESULTS: In patients with BRHP caused by bird breeding, budgerigar and parrot-specific IgG levels were significantly higher than in disease controls. Only parrot-specific IgG was significantly higher than in disease controls in patients caused by duvet use. However, among patients with acute episodes (acute and recurrent type of chronic BRHP), IgG antibodies against all three species were significantly higher than those of disease controls caused by bird breeding and the use of a duvet. CONCLUSIONS: Bird-specific IgG antibody with ImmunoCAP® was useful for screening and diagnosing BRHP caused by other bird species and duvets.

Antibody titers among healthcare workers for coronavirus disease 2019 at 6 months after BNT162b2 vaccination.

BACKGROUND: Antibody levels decrease substantially at 6 months after the BNT162b2 vaccine. The factors influencing titer of antibodies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among healthcare workers for coronavirus disease 2019 (COVID-19) is unclear. METHODS: We conducted a 6-month longitudinal prospective study in Japanese healthcare workers in a tertiary care hospital for COVID-19. Participants in the study were tested for the presence of anti-spike protein (SP) IgG antibodies before and at 1 and 6 months after the last vaccination dose. RESULTS: Among 1076 healthcare workers, 794 received the vaccine, and 469 entered the study. Five were infected with SARS-CoV-2 (none among COVID-19 section workers) by the end of the study and 451 participants were finally analyzed (mean age, 42.5 years; 27.3 % male; 18.8 % COVID-19 section workers). Median SP IgG index values were 0.0, 44.4, and 5.5 before and at 1 and 6 months after the last dose, respectively. Regression analysis revealed a negative correlation of SP IgG antibody levels with age (P < 0.0001), and higher levels in COVID-19 section workers (P = 0.0185) and in females (P = 0.0201). CONCLUSION: In healthcare workers at a COVID-19 hospital, IgG antibody titer was substantially lower at 6 months after receipt of the last dose of the BNT162b2 vaccine compared with that 1 month after the last dose, but was better preserved among younger participants, COVID-19 section workers and females.

Frequency and Significance of Coinfection in Patients with COVID-19 at Hospital Admission.

Objective Viral pneumonia is not rare in community-acquired pneumonia (CAP). Mixed or secondary pneumonia (coinfection) can be seen in viral pneumonia; however, its frequency in coronavirus disease 2019 (COVID-19) has only been investigated in a few studies of short duration, and its significance has not been fully elucidated. We investigated the frequency and significance of co-infection in patients with COVID-19 over a 1-year study period. Methods Coinfection was investigated via multiplex polymerase chain reaction (PCR), culture of respiratory samples, rapid diagnostic tests, and paired sera. We used logistic regression analysis to analyze the effect of coinfection on severity at admission and Cox proportional-hazards model analysis to analyze the effect of coinfection on need for high-flow nasal cannula, invasive mandatory ventilation use, and death, respectively. Patients We retrospectively investigated 298 patients who suffered CAP due to severe acute respiratory syndrome coronavirus-2 infection diagnosed by PCR and were admitted to our institution from February 2020 to January 2021. Results Primary viral pneumonia, and mixed viral and bacterial pneumonia, accounted for 90.3% and 9.7%, respectively, of COVID-19-associated CAP, with viral coinfection found in 30.5% of patients with primary viral pneumonia. Influenza virus was the most common (9.4%). Multivariable analysis showed coinfection not to be an independent factor of severity on admission, need for high-flow nasal cannula or invasive mandatory ventilation, and mortality. Conclusion Viral coinfection was common in COVID-19-associated CAP. Severity on admission, need for high-flow oxygen therapy or invasive mandatory ventilation, and mortality were not affected by coinfection.

Clinical Features of Fibrosing Mediastinitis in Japanese Patients: Two Case Reports and a Literature Review.

Fibrosing mediastinitis (FM) is a rare fibroinflammatory disease of the mediastinum with an etiology and clinical features that vary by world region. The characteristics of FM in Japan are still unknown. We herein report two Japanese patients with FM who were treated with corticosteroids and responded well. We also reviewed the Japanese literature on PubMed® and summarized the characteristics of 27 Japanese FM patients, including our two patients. In Japan, the predominant cases were those without a specific cause, were diffusely distributed, and responded well to corticosteroid therapy.

A retrospective analysis of pembrolizumab plus chemotherapy versus pembrolizumab monotherapy for advanced or recurrent non-small cell lung cancer.

BACKGROUND: Although clinical trials have investigated the addition of pembrolizumab to chemotherapy for non-small cell lung cancer, none have investigated the addition of chemotherapy to pembrolizumab. METHODS: We conducted a retrospective study of 71 NSCLC patients including 33 treated with pembrolizumab plus chemotherapy (combination therapy group) and 38 treated with pembrolizumab monotherapy (monotherapy group) from 1 May 2016 to 31 August 2020. RESULTS: Eleven of 33 (33.3%) patients in the combination therapy group and 37 of 38 (97.4%) patients in the monotherapy group had programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥50%. Objective response rate (ORR) and median overall survival (OS) were not significantly different between the combination therapy group and monotherapy group (54.5% vs. 47.4, p = 0.637 and 16.6 vs. 27.0 months, p = 0.463). In patients with PD-L1 TPS ≥50%, ORR and median OS were not different between the combination therapy group and the monotherapy group (63.6% vs. 48.6%, p = 0.499 and not reached vs. 27.0 months, p = 0.976). Thirty-three (100%) patients experienced adverse events (AEs) in the combination therapy group and 32 (84.2%) in the monotherapy group. Treatment discontinuation at 1 year due to AEs occurred more frequently in the combination therapy group (45.2%) than in the monotherapy group (21.1%). CONCLUSION: There was no significant difference in ORR and OS between the two groups, and treatment discontinuation was more frequent in the combination group. A randomized controlled trial is needed to evaluate the addition of chemotherapy to pembrolizumab for first-line treatment in patients with PD-L1 TPS ≥50%.

Screening and diagnosis of acute and chronic bird-related hypersensitivity pneumonitis by serum IgG and IgA antibodies to bird antigens with ImmunoCAP®.

BACKGROUND: Bird antigens are some of the most relevant antigens in hypersensitivity pneumonitis (HP). Possible sources of bird antigens are bird breeding, feather products and fertilizer with fowl droppings. For the screening and diagnosis of HP, the measurement of bird-specific antibodies should be standardized. The aim of this study was to clarify the utility of serum IgG (sIgG) and IgA (sIgA) antibodies to bird antigens in screening and diagnosing acute/chronic bird-related HP with ImmunoCAP® in multi-centre clinical research. METHODS: We executed a clinical performance test by conducting a multi-institutional study to measure the levels of sIgG/sIgA against pigeon, parrot and budgerigar antigens by the ImmunoCAP® system in 29 acute and 46 chronic bird-related HP patients. RESULTS: The levels of sIgG/sIgA against the bird antigens of the three species were significantly higher in subjects with acute bird-related HP and chronic bird-related HP with acute episodes (recurrent type) than in the control subjects. For sIgG, the optimal cutoff values by receiver operating characteristic (ROC) analysis were 24.6 mgA/L for pigeon, 14.0 mgA/L for parrot, and 8.7 mgA/L for budgerigar. By measuring multiple bird antigens and combining sIgG values of two species, the sensitivity and specificity for acute and recurrent-type chronic bird-related HP patients were 85-91% and 73-80%, respectively. For recurrent and insidious types of chronic bird-related HP, the sensitivity and specificity were 48-61% and 73-80%, respectively. CONCLUSIONS: Measurement of the levels of sIgG/sIgA against pigeon, budgerigar and parrot antigens by ImmunoCAP® was useful for screening and diagnosis in bird-related HP.

Clinical course and findings of 14 patients with COVID-19 compared with 5 patients with conventional human coronavirus pneumonia.

OBJECTIVE: To clarify what future problems must be resolved and how clinical findings of SARS-CoV-2 infection differ from those of cHCoV infection. METHODS: Patients and Methods Clinical characteristics of 14 patients with laboratory-confirmed Coronavirus disease 2019 (COVID-19) and 5 patients with cHCoV pneumonia admitted to our institution and treated up to March 8, 2020, were retrospectively analyzed. RESULTS: On admission, 10 patients had pneumonia, 5 of whom had pulmonary shadows detectable only via computed tomography (CT). During hospitalization, another patient with no pulmonary shadows on admission developed pneumonia. In total, 11 (78.6%) of the 14 patients developed pneumonia, indicating its high prevalence in COVID-19. During hospitalization, the patients' symptoms spontaneously relapsed and resolved, and gastrointestinal symptoms were frequently found. C-reactive protein values showed correlation with the patients' clinical courses. Ritonavir/lopinavir were administered to 5 patients whose respiratory conditions worsened during admission, all of whom improved. However, the pneumonia in the 6 other patients improved without antivirals. None of the 14 patients died, whereas 5 other patients with cHCoV pneumonia were in respiratory failure on admission, and one patient (20%) died. CONCLUSION: Both SARS-CoV-2 and cHCoV can cause severe pneumonia. Problems for future resolution include whether antiviral agents administered in cases of mild or moderate severity can reduce the number of severe cases, and whether antivirals administered in severe cases can reduce mortality.

Changes in airway diameter and mucus plugs in patients with asthma exacerbation.

BACKGROUND: Airway obstruction due to decreased airway diameter and increased incidence of mucus plugs has not been directly observed in asthma exacerbation. We studied the changes in the inner diameter of the airway (Din) and the frequency of mucus plugs by airway generation in patients with asthma exacerbation. We compared these patients to those in a stable phase using high-resolution computed tomography (HRCT). METHODS AND FINDINGS: Thirteen patients with asthma were studied by HRCT during asthma exacerbation and in a stable period. The HRCT study was performed on patients who could safely hold their breath for a short while in a supine position 1 hour after initial treatment for asthma exacerbation. Using a curved multiplanar reconstruction (MPR) software, we reconstructed the longitudinal airway images and the images exactly perpendicular to the airway axis to measure the Din and mucus plugs from the second- (segmental) to sixth-generation bronchi in all segments of the lungs.The ratios of Din (exacerbation/stable) were 0.91(P = 0.016), 0.88 (P = 0.002), 0.83 (P = 0.001), 0.80 (P = 0.001), and 0.87 (NS) in the second-, third-, fourth-, fifth-, and sixth-generation bronchi, respectively. The percentages of airway obstruction due to mucus plugs were notably higher in the fourth- and fifth-generation bronchi (17.9%/18.1% in stable phase and 43.2%/45.9% in the exacerbation phase, respectively) than in the other generations of bronchi. CONCLUSIONS: Among the bronchi examined, the fourth- and fifth-generation bronchi were significantly obstructed during asthma exacerbation compared with the stable phase in terms of a decreased airway diameter and mucus plugs.

Viral Pneumonia Requiring Differentiation from Acute and Progressive Diffuse Interstitial Lung Diseases.

Objective The clinical characteristics and chest imaging findings of viral pneumonia and several interstitial lung diseases (ILDs) overlap, and viral pneumonia may be underrecognized and misdiagnosed as certain ILDs. To clarify the frequency of viral pneumonia among patients with acute progressive clinical courses that required a differential diagnosis between ILDs and pneumonia, and to determine the most frequent ILDs misdiagnosed in cases of viral pneumonia. Patients and Methods We retrospectively analyzed patients hospitalized from 2010 to 2017 with an acute clinical course (≤30 days) who underwent bronchoalveolar lavage (BAL) for the differential diagnosis of infection and ILDs. We performed a multiplex PCR for respiratory viruses using the patients' preserved BAL fluid. The final diagnosis was made by a multidisciplinary approach and after considering the PCR results. The diagnosis at discharge was compared to the final diagnosis. Results Among the 109 patients, 53 were diagnosed with viral pneumonia. Viral pneumonia and other diseases showed some differences in symptoms and laboratory data; however, the differences were small or overlapped. Viral pneumonia was misdiagnosed on discharge as acute fibrinous organizing pneumonia, cryptogenic organizing pneumonia, or chronic eosinophilic pneumonia (AFOP/COP/CEP) (n=22), acute interstitial pneumonia (n=5), connective tissue disease-related ILDs (n=3), unclassifiable interstitial pneumonia (n=2), drug-induced ILD (n=1), and pneumonia (n=20). Conclusion Approximately half of the patients who underwent BAL had viral pneumonia. The most common ILD-related misdiagnoses were AFOP/COP/CEP. Differences in symptoms and laboratory findings between viral pneumonia and other diseases were small, and viral pneumonia should be included in the differential diagnosis when physicians encounter cases in which the abovementioned ILDs are suspected.

Allergic Bronchopulmonary Mycosis Caused by Schizophyllum commune: A Special Interest in Positive Culture of Other Basidiomycetes Fungi.

A 42-year-old man with asthma presented in 2007 with chest infiltration and productive cough. Pycnoporus sanguineus and Perenniporia tephropora were repeatedly isolated from sputum and bronchial washing fluids. Because we lacked immunologic evidence, we could not diagnose him with allergic bronchopulmonary mycosis (ABPM) due to these basidiomycetous fungi. At that time, serum-specific IgE and IgG against Schizophyllum commune findings were negative. Inhaled beclomethasone/salmeterol improved his condition. Seven years later, mucous plugs obtained via bronchoscopy at a relapse were compatible with allergic mucin. Because S. commune was isolated from mucous plugs and serum-specific IgG against S. commune turned positive, we diagnosed the patient with ABPM due to S. commune.

Diffuse alveolar hemorrhage caused by IgA deposition associated with multiple myeloma.

We report a man with diffuse alveolar hemorrhage caused by multiple myeloma who was diagnosed with the aid of bronchoalveolar lavage and transbronchial lung biopsy. Multiple myeloma should be considered as an important differential diagnosis in patients with diffuse alveolar hemorrhage, and bronchoscopy may help to differentiate the cause.

Restrictive ventilatory impairment improved by laminoplasty for ossification of the posterior longitudinal ligament.

We report a woman with severe restrictive ventilatory impairment because of respiratory muscle paralysis caused by ossification of the posterior longitudinal ligament (OPLL). Laminoplasty improved her respiratory function and quality of life. Cervical myelopathy including OPLL should be considered as an important differential diagnosis in patients with respiratory dysfunction.

Clinical characteristics and prognostic factors of pneumonia in patients with and without rheumatoid arthritis.

BACKGROUND: To elucidate the characteristics of pneumonia in rheumatoid arthritis (RA) patients and to assess whether pneumonia in RA patients differs from that in non-RA patients. METHODS: We retrospectively divided pneumonia patients into two groups, those with RA and those without RA, and compared the two groups. We evaluated the risk factors for mortality with univariate and multivariate logistic regression analysis. RESULTS: Among 1549 patients, 71 had RA. The RA patients with pneumonia were 71.0±8.9 years old, 54.9% were female, 40.9% had a smoking history, and 71.8% had underlying respiratory disease. Female sex, non-smoker, and respiratory comorbidities were statistically more frequent in the RA patients than non-RA patients. The most frequent causative microbial agents of pneumonia in the RA patients were Streptococcus pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, Mycoplasma pneumoniae, and influenza virus, whereas those of pneumonia in non-RA patients were S. pneumoniae, influenza virus, M. pneumoniae, Legionella spp., P. aeruginosa, H. influenzae, and Moraxella catarrhalis. Polymicrobial infection were identified as etiologies more frequently in the RA patients than non-RA patients. Although the severity of pneumonia did not differ between the two groups, mortality was statistically higher in the RA patients than non-RA patients. Multivariate analysis showed RA to be an independent risk factor for mortality. CONCLUSIONS: P. aeruginosa, H. influenzae, M. catarrhalis, and polymicrobial infection were statistically more frequent etiologies of pneumonia in the RA patients than non-RA patients. RA itself was found to be an independent risk factor for mortality from pneumonia.

Re-evaluation of the etiology and clinical and radiological features of community-acquired lobar pneumonia in adults.

OBJECTIVE: The aims of this study were to elucidate the frequency and etiology of community-acquired lobar pneumonia (CALP) and the clinical and radiological differences between CALP and tuberculous lobar pneumonia (TLP). PATIENTS AND METHODS: We retrospectively reviewed medical records of patients with community-acquired pneumonia (CAP) (n = 1032) and tuberculosis (n = 1101) admitted to our hospital. RESULTS: Sixty-nine (6.7%) patients with CAP and 23 (2.1%) with pulmonary tuberculosis developed CALP. Legionella species were the most common pathogen (27 patients, 39.1%), followed by Streptococcus pneumoniae (19 patients, 27.5%) and Mycoplasma pneumoniae (18 patients, 26.1%). Symptom duration was longer in the patients with TLP than in those with CALP. On chest radiographs, cavitation in the area of lobar pneumonia and nodular shadows were radiological findings predictive of TLP. High-resolution computed tomography showed cavitation in the area of lobar pneumonia, well-defined centrilobular nodules, and tree-in-bud sign to be the radiological findings predictive of TLP by multivariate logistic regression models. CONCLUSION: Common causes of CALP are Legionella species, S. pneumoniae, and M. pneumoniae. TLP should be considered in patients with lobar pneumonia, particularly in patients with long symptom duration, cavitation, and nodular shadows on chest radiographs, and cavitation, well-defined centrilobular nodules, and tree-in-bud sign on CT.

Allergic Bronchopulmonary Mycosis Due to Schizophyllum commune Treated Effectively with Voriconazole.

A 63-year-old woman presented to our hospital for cough, sputum, and abnormal shadows on chest X-ray. Schizophyllum commune was isolated from mucous plugs. Positive specific IgE and IgG against the fungi, elevated serum IgE, and mucous plugs with typical histologic findings of allergic bronchopulmonary mycosis (ABPM) led to the diagnosis of ABPM due to S. commune. We initially administered itraconazole unsuccessfully. Changing the antifungal agent to voriconazole resulted in improvement of the symptoms and chest imaging findings. Her ABPM has not relapsed for two years since the cessation of voriconazole, which was administered for one year.

Incidence and predictive factors of lung cancer in patients with idiopathic pulmonary fibrosis.

The incidence and risk factors of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) have been poorly investigated. We conducted a retrospective study of 632 patients with IPF to assess the incidence and risk factors of lung cancer development. Seventy patients developed lung cancer over a median follow-up period of 3.8 years. The incidence density of lung cancer development was 25.2 cases per 1000 person-years. The most frequent type was squamous cell carcinoma (30%), the majority developed lung cancer in the peripheral lung (82.9%) and adjacent to usual interstitial pneumonia (75.7%). In a multivariate Cox regression hazard model, pack-years of smoking ≥35 and coexisting emphysema were associated with lung cancer development. The 1-, 3- and 5-year all-cause mortality rates after lung cancer diagnosis were 53.5%, 78.6% and 92.9%, respectively. The incidence density of lung cancer is high in IPF patients and occurs more frequently in patients with smoking history of pack-years of smoking ≥35 and with coexisting emphysema. The majority of lung cancers develop adjacent to usual interstitial pneumonia. Knowledge of these factors may help direct efforts for early detection of lung cancer and disease management.

Smoking history and emphysema in asthma-COPD overlap.

BACKGROUND: Emphysema is a distinct feature for classifying COPD, and smoking history (≥10 pack-years) is one of several newly proposed criteria for asthma-COPD overlap (ACO). We studied whether or not a smoking history (≥10 pack-years) and emphysema are useful markers for classifying ACO and differentiating it from asthma with chronic airflow obstruction (CAO). METHODS: We retrospectively studied the mortalities and frequencies of exacerbation in 256 consecutive patients with ACO (161 with emphysema and 95 without emphysema) who had ≥10 pack-years smoking history, 64 asthma patients with CAO but less of a smoking history (<10 pack-years) and 537 consecutive patients with COPD (452 with emphysema and 85 without emphysema) from 2000 to 2016. In the patients with emergent admission, the causes were classified into COPD exacerbation, asthma attack, and others. RESULTS: No asthma patients with CAO had emphysema according to computed tomography findings. The prognoses were significantly better in patients with asthma and CAO than in those with ACO and COPD and better in those with ACO than in those with COPD. In both ACO and COPD patients, the prognoses were better in patients without emphysema than in those with it (P=0.027 and P=0.023, respectively). The frequencies of emergent admission were higher in COPD patients than in ACO patients, and higher in patients with emphysema than in patients without emphysema. ACO/emphysema (+) patients experienced more frequent admission due to COPD exacerbation (P<0.001), while ACO/emphysema (-) patients experienced more frequent admission due to asthma attack (P=0.014). CONCLUSION: A smoking history (≥10 pack-years) was found to be a useful marker for differentiating ACO and asthma with CAO, and emphysema was a useful marker for classifying ACO. These markers are useful for predicting the overall survival and frequency of exacerbation.

Clinical Characteristics of Influenza-Associated Pneumonia of Adults: Clinical Features and Factors Contributing to Severity and Mortality.

Background: Pneumonia is a major complication of influenza that contributes to mortality. Clinical characteristics and factors of influenza virus contributing to the severity and mortality of pneumonia have not been fully elucidated. Objective: The objective was to clarify clinical characteristics and factors contributing to the severity and mortality of influenza-associated pneumonia (flu-p). Methods: We retrospectively analyzed patients with flu-p. Results: From December 1999 to March 2016, 210 patients with a median age of 69 (range, 17 to 92) years with flu-p based on positive rapid antigen tests, increased antibody titers of paired sera, or positive results of reverse transcription polymerase chain reaction were admitted to our institution. A multivariate analysis found that advanced age (≥ 65 years), pneumonia subtypes (unclassified), diabetes mellitus, and acute kidney injury complicated with flu-p were independent factors associated with disease severity, whereas pneumonia subtypes (mixed viral and bacterial pneumonia and unclassified), healthcare-associated pneumonia, acute kidney injury complicated with flu-p, and severity on admission (severe) were independent factors associated with non-survival. Conclusion: The clinical characteristics of flu-p are varied, and the contribution of several factors to the severity and mortality of flu-p suggest their importance in either preventing flu-p or managing flu-p after it develops.