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.

New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation.

BACKGROUND: There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) are currently available. OBJECTIVE: This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods. METHODS: Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n = 37), chronic eosinophilic pneumonia (n = 64), Aspergillus-sensitized severe asthma (n = 26), or chronic pulmonary aspergillosis (n = 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey. RESULTS: The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively. CONCLUSIONS: The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.

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 aspergillosis in Japan: A nationwide survey.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by a hypersensitivity reaction to Aspergillus species colonizing the airways. The clinical characteristics of ABPA may differ depending on genetic and environmental background. We performed a nationwide survey to determine the clinical characteristics of ABPA in Japan. METHODS: In 2013, a questionnaire on physician-diagnosed ABPA/allergic bronchopulmonary mycosis was sent to 903 medical centers specializing in respiratory or allergic diseases. Cases fulfilling the following criteria were categorized as possible ABPA-central bronchiectasis (ABPA-CB): 1) presence of specific serum immunoglobulin E (IgE) antibodies or a positive skin reaction to Aspergillus, and 2) bronchiectasis or mucoid impaction in the central bronchi. RESULTS: Of 499 physician-diagnosed cases reported by 132 clinical centers, 358 cases met the criteria for possible ABPA-CB. Median age of ABPA-CB onset was 57 (interquartile range, 44-68) years; later-onset disease, developing ≥50 years of age, accounted for 66% of the cases and was associated with female sex, delayed onset of asthma, and lower levels of serum IgE. A third of the patients (120 patients, 34%) exhibited low levels of serum total IgE (<1000 IU/mL). Aspergillus species were isolated from sputum in 126/213 cases (59%), and Schizophyllum commune was identified in 12 (6%) patients. During the course of the treatment, ABPA recurred in 169 (48%) cases. CONCLUSIONS: This nationwide survey identified several unique clinical characteristics of ABPA in Japan, such as late-onset, relatively lower serum IgE levels, and frequent recurrences/flares.

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.

Acute ischaemic lung injury due to pulmonary vascular obstruction.

AIMS: We have encountered cases of a distinctive myxomatous alveolar wall thickening around pulmonary infarctions, and have termed it 'acute ischaemic lung injury' (AILI). In this study we determined if pulmonary infarction is the only cause of AILI and have elucidated its histological features. METHODS AND RESULTS: We examined 2941 cases that underwent lobectomy, surgical lung biopsies for nodular lesions or autopsies between 1994 and 2014. Cases were divided into pulmonary infarction and non-infarction groups. The histological features of AILI sought were lobule-based alveolar wall thickening (myxomatous or fibrous) with epithelial metaplasia and negligible inflammation. In order to characterize AILI further, we performed immunohistochemical staining using several antibodies. Thirty-four of 69 cases in the infarction group (mean age 57.1 years, 30 males) had AILI, whereas only one (but with vascular obstruction) of the remaining 2872 in the non-infraction group had AILI. AILI was located around infarctions. Separation of the epithelial and endothelial basement membranes of the alveolar wall was observed in 75% of cases. CONCLUSIONS: AILI is associated almost exclusively with lung infarction, caused presumably by vascular obstruction. We consider AILI to represent a distinct lung lesion other than pulmonary haemorrhage and infarction.

Risk factors for the severity and mortality of pneumococcal pneumonia: Importance of premorbid patients' performance status.

Comorbidity is known to be associated with the severity and mortality of pneumonia. The severity of each underlying disease varies, and performance status, which is known to be a prognostic factor of malignant diseases, reflects the overall patient condition as affected by his/her comorbidity and underlying diseases of various severity. We investigated whether premorbid patients' performance status is associated with the severity and mortality of pneumococcal pneumonia. This retrospective study assessed these factors in hospitalized patients suffering from pneumococcal pneumonia from 2002 to 2015. We included 424 patients aged 68.9 ± 14.1 years in the study, of which 68.9% were men. A multivariate analysis found that advanced age (≥65 years), diabetes mellitus, and poor performance status were independent factors associated with severity, whereas old pulmonary tuberculosis, poor performance status, pneumococcal bacteremia, and severe pneumonia were independent factors that were associated with non-survival. Poor performance status was associated with the severity and mortality of pneumococcal pneumonia.

[A case of Lemierre's syndrome with septic pulmonary embolisms].

A 41-year-old-man with sore throat and fever visited a nearby clinic. He was given antibiotics, but on disease day 11, the left side of his neck had swollen. Because chest CT on disease day 16 showed bilateral multiple pulmonary nodules, he was admitted to our hospital. He had septic pulmonary embolisms and thrombophlebitis of the left internal jugular vein, and Fusobacterium necrophorum was isolated from the blood and neck pus culture, and we diagnosed him as having Lemierre's syndrome. We administered piperacillin/ tazobactam and heparin, and his symptoms improved thereafter. Lemierre's syndrome is relatively rare but is increasing in recent years. We report herein this case and compare reported cases in Japan with those from overseas.

Prognostic factors of 634 HIV-negative patients with Mycobacterium avium complex lung disease.

RATIONALE: The prognostic factors of Mycobacterium avium complex lung disease (MAC-LD) are not clearly defined. OBJECTIVES: To assess the prognostic factors of all-cause and MAC-specific mortality in patients with MAC-LD, especially in accordance with radiographic features, first-line treatment, and host predisposition. METHODS: Medical records of 634 HIV-negative patients with MAC-LD treated at our institution in Saitama, Japan were retrospectively analyzed. MEASUREMENTS AND MAIN RESULTS: Patients' mean age was 68.9 years, and median follow-up period was 4.7 years. Radiographic features included nodular/bronchiectatic (NB) disease: 482 patients (76.0%); fibrocavitary (FC) disease: 105 patients (16.6%); FC+NB disease: 30 patients (4.7%); and other types: 17 patients (3.0%). First-line treatments were observation or one drug: 479 patients (75.6%); 2 to 5 drugs: 131 patients (20.7%); and unknown: 24 patients (3.8%). A multivariate Cox proportional hazard model showed male sex, older age, presence of systemic and/or respiratory comorbidity, non-NB radiographic features, body mass index (BMI) less than 18.5 kg/m(2), anemia, hypoalbuminemia, and erythrocyte sedimentation rate greater than or equal to 50 mm/h to be negative prognostic factors for all-cause mortality, and FC or FC+NB radiographic features, BMI less than 18.5 kg/m(2), anemia, and C-reactive protein greater than or equal to 1.0 mg/dl to be negative prognostic factors for MAC-specific mortality. CONCLUSIONS: The first-line treatment regimen was not associated with all-cause mortality. FC or FC+NB disease, BMI less than 18.5 kg/m(2), and anemia were negative prognostic factors for both all-cause and MAC-specific mortality.

Magnetic resonance imaging can detect thoracic inflammation due to familial Mediterranean fever.

A 32-year-old man presented to our hospital complaining of periodic fever and unilateral chest pain. We suspected that he had familial Mediterranean fever because of his symptoms. Magnetic resonance imaging (MRI) showed an increased intensity within the anterior chest wall, which was consistent with the site of his pain. Genomic analysis showed the patient to be heterozygous for the E148Q/M694I mutation in the MEFV gene, and we diagnosed familial Mediterranean fever. The ability of MRI to detect inflammatory changes could provide useful additional information for evaluating thoracic symptoms in FMF patients, and the detection of inflammatory changes using MRI may aid in early diagnosis, thus contributing to early and adequate treatment.

Airway dimensions and pulmonary function in chronic obstructive pulmonary disease and bronchial asthma.

BACKGROUND AND OBJECTIVE: COPD and bronchial asthma are chronic airway diseases with a different pathogenesis. Comparisons of differences in airway calibre by bronchial generation between these diseases and their importance to pulmonary function have not been fully studied. We investigated airway calibre and wall thickness in relation to pulmonary function in patients with asthma, COPD, asthma plus emphysema and normal subjects using CT. METHODS: Sixty-three asthmatic patients, 46 COPD, 23 patients with asthma plus emphysema and 61 control subjects were studied cross-sectionally. We used a software with curved multiplanar reconstruction to measure airway dimensions from 3rd- to 6th-generation bronchi of the right lower posterior bronchus. RESULTS: Patients with COPD had increased wall thickness, but the airway was not narrow from the 3rd-(subsegmental) to 6th-generation bronchi. Mean bronchial inner diameter (Di) of 3rd- to 6th-generation bronchi in patients with asthma or asthma plus emphysema was smaller than that of COPD patients and normal subjects. Airway luminal area (Ai) of 5th-generation bronchi most closely correlated with pulmonary function in patients with stable asthma. Although Di was similar in patients with asthma and asthma plus emphysema, the Ai of 6th-generation bronchi correlated significantly with pulmonary function in patients with asthma plus emphysema. CONCLUSIONS: Airway calibre in asthma may be smaller than in COPD. Airflow limitations correlated more closely with peripheral Ai in patients with asthma plus emphysema than in patients with asthma alone.

Adenovirus pneumonia in an immunocompetent adult.

Adenovirus pneumonias are reported relatively commonly in pediatric or immunocompromised patients, but the clinical presentation of adenovirus pneumonia in immunocompetent hosts is not well known. We treated an immunocompetent 42-year-old man with mild adenovirus pneumonia following pharyngitis and conjunctivitis. Diagnosis was established on the basis of chest radiologic findings, detection of adenovirus type 7 DNA by PCR assay in material obtained from bronchoalveolar lavage (BAL), and a greater than fourfold rise in adenovirus-specific antibody titers during the course of illness. The patient's self-limiting symptoms improved within 2 weeks, and chest radiologic findings improved within 4 weeks. PCR assay of material obtained by BAL was useful for the rapid diagnosis of adenovirus pneumonia.

Antigen avoidance and outcome of nonfibrotic and fibrotic hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is classified into nonfibrotic and fibrotic phenotypes. Patients with nonfibrotic HP often experience recurrence and develop fibrosis, whereas those with fibrotic HP have a poor prognosis. Although antigen avoidance has long been the first line of treatment for HP, its impact on prognosis has been poorly reported. METHODS: Medical records of 121 patients with HP diagnosed by new diagnostic criteria of American Thoracic Society/Japanese Respiratory Society/Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) guidelines and treated at our institution in Saitama, Japan, were retrospectively analysed. HP was classified into nonfibrotic and fibrotic phenotypes and six HP subtypes: summer-type, bird-related, home-related and occupational HP, humidifier lung, and hot tub lung. Achievement of reduced exposure to inciting agents was divided into complete antigen avoidance (CAA) and incomplete antigen avoidance (IAA) by HP subtype. RESULTS: Of the 74 patients with nonfibrotic HP, 30 achieved CAA and experienced no recurrence or development of fibrosis. In the remaining 44 patients with IAA, 24 (54.5%) experienced recurrence and/or development of fibrosis. The all-cause 5-year mortality rate in the 47 patients with fibrotic HP was 47.8%. Negative prognostic factors of HP-related mortality in these patients were <50% lymphocytes in bronchoalveolar lavage (BAL) and honeycombing. Multivariate analysis showed a tendency for IAA to be related to poorer survival (hazard ratio 3.452, 95% CI 0.964-12.359, p=0.057). CONCLUSIONS: In the patients with nonfibrotic HP, CAA resulted in no recurrence or development of fibrosis and longer survival. In the patients with fibrotic HP, <50% lymphocytes in BAL and honeycombing were negative prognostic factors for mortality.

Significance of Hypophosphatemia in Patients with Pneumonia.

Objective Phosphate is a fundamental element involved in a number of physiological pathways. A previous study showed abnormal laboratory findings and a higher mortality in hypophosphatemic patients than in normophosphatemic patients with pneumonia. Sporadic cases of pneumonia due to Legionella spp., Streptococcus pneumoniae, and viruses have been reported; however, the significance of hypophosphatemia in patients with pneumonia has not been adequately studied. We determined whether or not hypophosphatemia in patients with community-acquired pneumonia (CAP) was associated with specific pathogens, patient factors, disease severity, and mortality. Method We retrospectively analyzed 600 patients with CAP who were admitted to our hospital between January 1, 2010, and December 31, 2019. Results Hypophosphatemia was found in 72 (12.0%) of the 600 patients. The most frequent causative microbial agents of CAP in patients with hypophosphatemia were S. pneumoniae, Legionella spp., and influenza virus, whereas in severely ill patients with hypophosphatemia, influenza virus was the most common. Legionella spp., diabetes mellitus, and severe pneumonia were the independent factors for hypophosphatemia in the multivariable analysis. An impaired performance status, severe status on admission, interstitial pneumonia, bacteremia, and guideline-discordant therapy were the independent factors associated with mortality in the multivariable analysis. Hypophosphatemia was not significantly associated with mortality but showed a trend towards higher mortality in the multivariable analysis. Conclusion Hypophosphatemia was not associated with the prognosis in patients with CAP. However, the significance of hypophosphatemia for clinicians lies in the laboratory findings that predict abnormal glucose metabolism, Legionella infection, and severe disease.

Comparison of high-dose salmeterol/fluticasone and moderate-dose salmeterol/fluticasone plus low-dose mometasone in patients with severe persistent asthma.

BACKGROUND AND OBJECTIVE: The effects of adding a second inhaled corticosteroid with a different particle size, compared with using an increased dose of a single inhaled corticosteroid, were assessed in patients with persistent asthma. METHODS: This was an open-label study of Japanese asthma patients over 20 years of age. After a 1-month run-in period, 36 patients with inadequate control while using salmeterol/fluticasone propionate 50/250 µg (SFC50/250) bd, were randomized to receive SFC50/500 bd or SFC50/250 plus mometasone 100 µg bd (SFC50/250/MF100) for 2 months. RESULTS: Both treatments resulted in improvements in morning and evening PEF. There were no significant changes in FEV(1) , maximum mid-expiratory flow, maximum expiratory flow rate at 50%, maximum expiratory flow rate at 25% or exhaled NO (FENO) in the SFC50/500 group. On the other hand, there were significant improvements in FEV(1) % (+12.2%, P = 0.0142), %maximum mid-expiratory flow (+28.9%, P = 0.0181), %MEF50 (+32.4%, P = 0.0206) and %MEF25 (+30.3%, P = 0.0113) in the SFC50/250/MF100 group. The changes in FENO (-23.2% (P = 0.0157) in the SFC50/250/MF100 group and -14.5% (not significant) in the SFC50/500 group) did not differ significantly between the groups. CONCLUSIONS: In patients with severe persistent asthma, addition of low-dose mometasone to SFC50/250 improved spirometric parameters, FENO and PEF, while an increase in dose from SFC50/250 to SFC50/ 500 only improved PEF.

[Legionella pneumonia in a patient with positive culture results of Legionella pneumophila serotype 1 from bronchoalveolar lavage fluid but negative urinary antigen test results].

A 39-year-old man presented to a local physician complaining of fever, headache without cough or sputum. Abnormal shadows were found on chest X-ray films. Pneumonia was diagnosed and he was referred to our hospital, where chest computed tomography showed bilateral, multifocal, and patchy ground-glass opacities. Neither the urinary antigen test for Streptococcus pneumoniae nor that for Legionella was positive. Because he had visited a public spa several days before developing the fever and headache, and because hypophosphatemia was identified, we then suspected Legionella pneumonia. Bronchoalveolar lavage fluid yielded positive culture of Legionella pneumophila serotype 1. The Legionella urinary antigen is known to detect Legionella pneumophila serotype 1 infection; however, sensitivity and specificity of the test are 60-95% and > 99%, but care should be taken when urinary antigen test results are negative in suspected cases of Legionella pneumophila serotype 1 pneumonia. In the present case, bronchoalveolar lavage fluid was a useful method for diagnosing Legionella pneumonia.

[A case of organizing pneumonia which recurred 51 months after radiotherapy following breast-conserving surgery].

A 54-year-old woman who had undergone breast-conserving surgery followed by irradiation presented to a local physician after developing a cough and low-grade fever 9 months after radiation therapy. She was given a diagnosis of pneumonia and antibiotics were administered, but since she did not improve, she was transferred to our hospital. We performed lung biopsy via thoracoscopy and diagnosed organizing pneumonia based on pathological findings. Steroid administration based on her chest X-ray findings, improved her condition. After discharge, her steroid dose was tapered on an outpatient basis, but she suffered relapse of her organizing pneumonia three times. The prednisolone dose at relapse was 10 mg/day at 20 months, 7.5 mg/day at 36 months, and 7 mg/day at 51 months after radiation therapy, respectively. Organizing pneumonia that develops after irradiation following breast-conserving surgery has been known to occasionally relapse, and to the best of our knowledge the final relapse reported here, 51 months after radiation therapy is the longest relapse reported.

[Type A influenza pneumonia with diffuse alveolar damage diagnosed by increased antibody titers and immunohistochemical staining].

A 58-year-old man presented to a local physician with cough, fever, myalgia and dyspnea. His chest X-ray film showed abnormal shadows and therefore he was admitted to our hospital. Chest computed tomography showed bilateral ground-glass opacities and bilateral consolidation. We suspected influenza pneumonia, but the results of both an influenza rapid antigen test and reverse transcriptase-polymerase chain reaction test for novel influenza (H1N1 2009) were negative. Transbronchial lung biopsy showed diffuse alveolar damage patterns. We diagnosed acute interstitial pneumonia and initiated corticosteroid therapy. Moreover, because influenza pneumonia could not be excluded according to his clinical picture, oseltamivir was administered. His condition improved and he was discharged. After discharge, the levels of antibody titers for influenza A virus significantly increased. We therefore re-evaluated his transbronchial lung biopsy specimen and found that immunohistochemical staining was positive for influenza A antigen in his bronchial and bronchiolar cells. We re-diagnosed his condition as influenza pneumonia. The possibility that influenza pneumonia may present in cases originally diagnosed as acute interstitial pneumonia must be considered.