Findings from a discontinued clinical trial of favipiravir in high-risk patients with early-onset COVID-19.

INTRODUCTION: Favipiravir terminates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Accordingly, early administration of favipiravir to SARS-CoV-2-infected coronavirus disease 2019 (COVID-19) patients may be expected to suppress disease progression. METHODS: A randomized double-blind placebo-controlled trial was conducted to demonstrate efficacy of favipiravir in reducing disease progression in patients with mild COVID-19. The participants were unvaccinated patients with comorbidities and at risk of progression to severe disease. Patients were enrolled within 72 h of disease onset and randomized to receive either favipiravir (1800 mg/dose on Day 1 followed by 800 mg/dose) or matching placebo twice daily for 10 days. The primary endpoint was the proportion of patients requiring oxygen therapy within 28 days of randomization. RESULTS: The trial was discontinued after enrolling 84 patients due to slower than anticipated enrollment caused by rapid uptake of SARS-CoV-2-vaccines and the emergence of the Omicron variant. Results from the 84 patients demonstrated no significant difference in all clinical outcomes. In post-hoc analyses, favipiravir treatment showed higher efficacy in patients within 48 h of onset. No deaths or severe adverse events were documented in the favipiravir group. Plasma concentrations of favipiravir from Day 2 onward were maintained above 40 µg/mL. CONCLUSIONS: Conducting clinical trials for pathogens like SARS-CoV-2 that rapidly accumulate mutations leading to altered disease characteristics carries significant risks unless it can be done in a short period. Therefore, it would be important to prepare the comprehensive clinical trial platform that can appropriately and promptly evaluate drugs even under a pandemic.

Grade 4 asbestosis does not extend directly from the respiratory bronchiole to the peripheral lung.

AIMS: To confirm whether or not grade 4 asbestosis progresses from the respiratory bronchiole to the peripheral lung. METHODS AND RESULTS: We examined retrospectively the autopsy or lobectomy specimens from 31 cases (29 males; mean age 64 years) satisfying the pathological criteria of grade 4 asbestosis. Asbestos bodies (ABs) were quantified in samples of dissolved lung and in tissue preparations on glass slides. Respiratory bronchiolar lesions were graded as 0, 1 and ≥2. Grade 4 asbestosis was subdivided into an atelectatic induration (AI) and usual interstitial pneumonia pattern (UIP pattern). Five, 10, and 16 cases had grades 0, 1 or ≥2 lesions, respectively, with mean respective numbers of ABs in dissolved lung of 117 000/g dry lung, 468 000/g and 968 000/g; and in specimens on glass slides of seven ABs/cm2 of tissue slice, 34 ABs /cm2 and 195 ABs /cm2 . The differences were significant. Fifteen and 16 cases showed AI and UIP patterns, respectively, with mean respective numbers of ABs in dissolved lung of 1 006 000/g dry lung and 354 000/g, and 186 and 56 ABs/cm2 on glass slides. The differences were significant. AI patterns originated in subpleural lobules or subpleural zonal areas and UIP patterns originated in subpleural, peripheral lobules. CONCLUSIONS: Grade 4 asbestosis does not start in the respiratory bronchiole. The presence of a grade 1 lesion is not required for the diagnosis of grade 4 asbestosis.

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.

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.

Asbestos exposure increases the incidence of histologically confirmed usual interstitial pneumonia.

AIMS: We hypothesized that asbestos exposure increases the incidence of macroscopically visible and histologically confirmed usual interstitial pneumonia (histological UIP). METHODS AND RESULTS: We retrospectively examined 1718 cases (1202 males; mean age 66.7 years) who underwent lobectomy for resection of pleuropulmonary tumours. Objective markers for asbestos exposure included: the presence of malignant pleural mesothelioma, the presence of pleural plaques (PPs) and asbestos bodies in the histological specimen. Risk factors for histological UIP were examined. Two separate groups were studied: 183 with asbestos exposure, and 239 with histological UIP. The 183 cases with asbestos exposure had higher rates of positive occupational history and histological UIP (31%) than the remaining 1535. Among the asbestos-exposed group, small numbers of asbestos bodies were found in histological specimens of 21 cases of histological UIP. PPs and asbestos bodies were more frequent in the 239 patients with histological UIP than in the remaining 1479 UIP-negative patients. Multivariate analysis showed that asbestos exposure, especially positivity for asbestos bodies, that does not meet the current criteria for asbestosis increases the risk of histological UIP (P < 0.0001). CONCLUSIONS: Asbestos exposure causes asbestosis and increases the incidence of histological UIP.

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.

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.

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.

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.

[Clinical study of pneumocystis pneumonia in patients with rheumatoid arthritis].

We reviewed case of pneumocystis pneumonia (PCP) with rheumatoid arthritis. We administered the antirheumatic drug methotrexate (MTX) at the time of to 13 patients, corticosteroids to 11 patients and a tumor necrosis factor (TNF) inhibitor to 3 patients. Treatment for PCP was started on admission in all cases. We administered adrenocorticosteroids to all 13 patients with a PaO2 level < 70 Torr. Three patients were under respiratory management, and 4 patients died. By univariate analysis, prognostic indicators of death were: presence of acute respiratory distress syndrome (ARDS), peripheral blood neutrophil/lymphocyte ratio, serum albumin value, serum beta-D-glucan value, and AaDO2 and PaO2/FiO2 ratios. Readministration of a TNF inhibitor in 2 patients and MTX in 3 patients was possible after PCP remission. Even though we began treatment for PCP on the day of admission, 25% of patients died. PCP may occur in patients who are given MTX or a TNF inhibitor or both, and the clinician should endeavor to detect its onset as early as possible. Elucidation of the prognostic indicators of recovery may require multivariate analysis of many cases.

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%.

Outcome and risk factor of immune-related adverse events and pneumonitis in patients with advanced or postoperative recurrent non-small cell lung cancer treated with immune checkpoint inhibitors.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with pre-existing respiratory diseases have been excluded in clinical trials of immune checkpoint inhibitor (ICI) therapy, and it is unknown whether the same degree of response can be expected as that in patients without pre-existing respiratory diseases and if they are associated with increased risk for various immune-related adverse events (irAEs) and ICI pneumonitis. This study aimed to evaluate predictive factors of clinical response, prognostic factors, risk factors of irAEs, and ICI pneumonitis in NSCLC patients with or without pre-existing respiratory diseases. METHODS: We conducted a retrospective study of 180 NSCLC patients who received ICI monotherapy of nivolumab, pembrolizumab, or atezolizumab from 1 January 2016 to 31 March 2019. RESULTS: A total of 119 patients had pre-existing respiratory diseases, including 20 with pre-existing idiopathic interstitial pneumonias (IIPs). A total of 85 patients experienced irAEs, of which ICI pneumonitis was the most frequent adverse event, occurring in 27 patients. Of the three patients who died from irAEs, all from ICI pneumonitis, two had pulmonary emphysema and one had pre-existing IIP. In multivariate analyses, irAEs were associated with objective response rate (ORR) and favorable OS, and IIPs were associated with increased risk for ICI pneumonitis. However, IIPs were not associated with low ORR or poor OS. CONCLUSIONS: Pre-existing IIPs were a risk factor for ICI pneumonitis. However, this study showed that ICI therapy can be offered to patients with pre-existing respiratory diseases with the expectation of the same degree of response as that in patients without pre-existing respiratory diseases. KEY POINTS: Significant findings of the study: Pre-existing IIPs were a risk factor for ICI pneumonitis, but objective response rate and prognosis of patients with IIPs were similar to those of other patients. WHAT THIS STUDY ADDS: In patients with pre-existing IIPs, ICI pneumonitis should be noted. However, ICI therapy can be offered to patients with pre-existing respiratory diseases with the expectation of the same degree of response as that in patients without pre-existing respiratory diseases.

The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: In this study the prevalence, lung function and prognosis of IPF combined with emphysema were evaluated. METHODS: Consecutive patients with usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT), with or without emphysema, were assessed retrospectively. The area of fibrosis in the base of the lungs was assessed by HRCT as minimal (<2 cm from the subpleura), moderate (>or=2 cm from the subpleura, <1/3 of the area of the base of the lungs) or severe (>or=1/3 of the area of the base of the lungs). RESULTS: Among 660 patients with UIP on HRCT, 221 showed upper-lobe emphysema. Pulmonary function results for patients with UIP and UIP/emphysema, respectively, were: FVC, 71.8% and 87.1%; FEV1%, 86.7% and 87.9%; and DL(CO), 74.3% and 65.2% of predicted. The relationship between FVC, the extent of fibrosis and survival was investigated in 362 patients with records of pulmonary function tests and no lung cancer at the time of entry into the study. Although the extent of fibrosis was similar between the groups, 71.3% of UIP patients met the lung volume criteria for IPF (FVC <80% of predicted), whereas only 26.5% of UIP/emphysema patients met the lung volume criteria for IPF. Median survival was 7.5 years in the UIP group and 8.5 years in the UIP/emphysema group. CONCLUSIONS: Emphysema was a common finding in patients with UIP. Patients with UIP and emphysema had greater lung volumes and better survival compared with those with UIP alone.

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.

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 lung function and health status in patients with COPD treated with tiotropium or salmeterol plus fluticasone.

BACKGROUND AND OBJECTIVE: The effects of tiotropium, a long-acting anticholinergic drug, were compared with those of the combination of salmeterol, a long-acting beta(2)-agonist, and fluticasone, an inhaled corticosteroid, in patients with COPD. METHODS: A 4-month, randomized, open cross-over study of tiotropium, 18 microg once daily, versus salmeterol, 50 microg, plus fluticasone, 200 microg, twice daily, was conducted in patients with COPD. Efficacy was assessed by spirometry and responses to the St George's Respiratory Questionnaire (SGRQ). After 4 months, patients were asked to select their subsequent therapy and indicate the reasons for their selection. RESULTS: A total of 78 patients completed the study. There were no significant differences in the improvements in FEV(1) or SGRQ scores between the therapies. Similar numbers of patients selected tiotropium (42.3%) and salmeterol plus fluticasone (57.7%). However, those who preferred one of the therapies demonstrated greater improvements in SGRQ scores with that therapy. One subgroup of patients (30.8%) showed greater improvements in dyspnoea and FEV(1) in response to tiotropium, and the other subgroup of patients (35.9%) showed greater improvements in dyspnoea and FEV(1) in response to salmeterol plus fluticasone. Some patients (14.1%) selected salmeterol plus fluticasone because of positive effects on sputum expectoration. CONCLUSIONS: The study was unblinded and the results need to be interpreted with caution. However, tiotropium and salmeterol plus fluticasone had similar overall effects on pulmonary function and SGRQ scores in patients with COPD. Responses to the two therapies were heterogeneous, and the patients who showed greater improvements in FEV(1) or SGRQ scores with one of the therapies preferred it for their subsequent treatment.

[A case of pulmonary Mycobacterium scrofulaceum infection and review of the tendency towards recent acid-fast bacilli infection].

A 47-year-old man presented to a local physician with a chief complaint of sputum and cough for 3 months. Chest X-ray showed bilateral consolidation in the upper lung fields, and the patient was suspected to have pulmonary tuberculosis: he was then referred to our hospital. Smear and culture of both sputum and gastric juice showed acid-fast bacilli, and we started administration of rifampicin, isoniazid, ethambutol, and pyrazinamide. Results of the culture and identification test showed the causative bacillus to be Mycobacterium scrofulaceum (M. scrofulaceum). We stopped pyrazinamide and added clarithromycin to the treatment regimen, which resulted in symptomatic relief and radiological improvement. The frequency of pulmonary nontuberculous mycobacteriosis is increasing: in contrast, pulmonary infection by M. scrofulaceum has been decreasing. Nevertheless, M. scrofulaceum infection should be considered in the differential diagnosis from tuberculosis when the results of radiological findings and sputum culture suggest pulmonary tuberculosis.

[Nemaline myopathy detected with respiratory failure and right ventricular heart failure].

We describe the case of a 40-year-old woman who was admitted for dyspnea and pitting edema of the lower extremities. Severe type II respiratory failure and right ventricular heart failure were present. Non-invasive positive pressure ventilation (NIPPV) improved the symptoms and blood gas values. Since the results of respiratory function tests and computed tomography indicated neuromuscular disease, muscle biopsy was performed and nemaline myopathy was diagnosed. NIPPV was necessary due to severe hypoxia and hypercapnia caused by severe hypoventilation during sleep; however, daytime NIPPV was stopped within a few days, and the patient was discharged with instructions to continue NIPPV at night only. Since discharge, she has been followed-up on an outpatient basis for 8 years. Adult-onset nemaline myopathy with respiratory failure and right ventricular heart failure as presenting features is rare, and NIPPV can be useful in such cases.