Exacerbation rates in Japanese patients with obstructive lung disease: A subanalysis of the prospective, observational NOVELTY study.

BACKGROUND: Although clinical trials including asthma and COPD patients have revealed much about exacerbation frequencies, most studies are limited in that they recruited patients only with a clear diagnosis of one disease or the other, based on conventional diagnostic criteria, which may exclude many real-world patients with mixed symptoms. METHODS: NOVELTY is a global prospective observational study of patients with asthma and/or COPD from real-world practice. In this subanalysis, we compared patient characteristics of obstructive pulmonary diseases between the Japanese population (n = 820) and the overall population excluding Japanese patients (n = 10,406). RESULTS: The Japanese population had fewer exacerbations than the overall population across most of the physician-assessed disease severities and all diagnoses. The difference in exacerbation frequencies was more prominent in patients with COPD and asthma + COPD. The Japanese population was older, had higher former smoking rates, lower BMI, fewer respiratory symptoms, and better health-related quality of life compared with the overall population across all diagnoses. CONCLUSIONS: We clarified differences in patient characteristics among patients with asthma and/or COPD in Japan compared with non-Japanese patients. Importantly, we found that Japanese patients with asthma and/or COPD had significantly fewer exacerbations compared with patients overall. The results from our study may contribute to the development of precision medicine and guidelines specific to Japan.

[THE MINIMUM NUMBER OF SPUTUM SMEAR SAMPLES NEEDED FOR THE DIAGNOSIS OF TUBERCULOSIS].

[Objective] To determine whether three sputum examinations with fluorescent staining are necessary to diag- nose tuberculosis (TB) in our hospital. [Patients] From April 2005 to December 2012, 379 TB patients were admitted and received anti-TB therapy in our hospital. [Methods] A retrospective study was conducted to assess the positivity rates of sputum smears based on three exami- nations. The positivity rate of first sputum smear and the cumulative smear-positive rates in the second and third were determined. Then, we also determined difference of positivity rates in sputum properties, sampling procedures and cavity formation. [Results] Of the 379 patients who met the screening criteria, 300 tested positive based on the first sputum smear (79.2%). The positivity rate of the first sputum smears was higher in the purulent sputum group than in the mucous sputum group (91.2% vs. 72.3%). Cavity formation, and sputum extraction procedures were not related to the positivity rate of the first sputum smears. In the mucous sputum group, the cumulative smear-positive rate in the second test significantly rose, but did not rise in the third test. [Conclusions] Three sputum smear examinations were necessary in patients who submitted mucous sputum samples. It is important to get purulent sputum.

[AN OUTBREAK OF PULMONARY TUBERCULOSIS DUE TO DEFINITE EXOGENOUS REINFECTION AMONG ELDERLY INDIVIDUALS IN WELFARE FACILITIES].

PURPOSE: We report an outbreak of 64 cases of tuberculosis (TB) that spread in a welfare facility for elderly individuals. OBJECTIVE AND METHODS: First, 64 TB patients who had contact with the source patient were screened at our hospital. We examined the time course up to the discovery of symptoms and analyzed the results for variable numbers of tandem repeats (VNTR) and the drug susceptibility tests. Second, we performed chest computed tomography to examine lesions due to a previous TB infection. RESULT: The source patient had recurrent aspiration pneumonia. The delay in doctor consultation was considered day 0, and the delay of diagnosis was 267 days. On examining the contacts, we found that 29 patients had TB while 35 had a latent TB infection. Results of the VNTR and the drug susceptibility tests showed that all the patients who developed TB had the same pattern as that of the source patient. Chest computed tomography showed lesions due to a previous TB infection in 8 patients. CONCLUSION: Based on the results of the VNTR and drug susceptibility tests, we concluded that the outbreak was due to an exogenous infection from the same source. All 8 patients who showed lesions due to a previous TB infection were aged > 81 years, and TB in these patients was found to be due to exogenous re-infection.

Low-intensity noninvasive ventilation: Lower pressure, more exacerbations of chronic respiratory failure.

BACKGROUND: For patients with chronic respiratory failure (CRF) who are treated with noninvasive positive pressure ventilation (NPPV), a little is known regarding the effects of low-intensity NPPV (LI-NPPV) on the clinical course of CRF and the frequency of adjustments in these patients. OBJECTIVES: This study investigated the effects of LI-NPPV on the clinical course of patients with CRF as compared with patients who were treated with conventional NPPV (C-NPPV) and determined how frequently NPPV was adjusted during therapy. METHODS: Clinical data from 21 patients who received long-term NPPV were retrospectively analyzed. Patients were categorized into two groups based on the level of initial pressure support (PS): C-NPPV group (PS ≥ 10 cm H2O) and LI-NPPV group (PS < 10 cm H2O). RESULTS: Patients in the LI-NPPV group had significantly more exacerbations of CRF (P < 0.05). There was no significant difference in the number of patients who required adjustments of NPPV settings between the two groups. There was no significant difference in PaCO2 levels 1 month after the start of NPPV between the two groups; however, PaCO2 levels were significantly lower after 1 year in the C-group (P < 0.001). Seventy-one percent of LI-NPPV patients and 43% of C-NPPV patients needed NPPV adjustments. CONCLUSIONS: Attention should be paid to CRF patients who are initially administered LI-NPPV; they should be carefully observed because they can develop more exacerbations of CRF than patients undergoing C-NPPV. If possible, higher initial PS should be administered to prevent CRF exacerbations.

Effect of Asian dust on pulmonary function in adult asthma patients in western Japan: A panel study.

BACKGROUND: Asian dust (AD) has become a major health concern. The concentration of AD is typically expressed in particulate matter less than 10 µm (PM10) and 2.5 µm (PM2.5). However, PM10 and PM2.5 consist of various substances besides AD. Light detection and ranging (LIDAR) systems can selectively measure the quantity of AD particles to distinguish non-spherical airborne particles from spherical airborne particles. The objective of this study was to investigate the relationship between pulmonary function in adult asthma patients and AD using LIDAR data. METHODS: Subjects were 231 adult asthma patients who had their morning peak expiratory flow (PEF) measured from March to May 2012. A linear mixed model was used to estimate the association of PEF with sand dust particles detected by LIDAR. RESULTS: Increases in the interquartile range of AD particles (0.018 km(-1)) led to changes in PEF of -0.42 L/min (95% confidence interval [CI], -0.85 to 0.01). An increase of 11.8 µg/m(3) in suspended particulate matter and 6.9 µg/m(3) in PM2.5 led to decreases of -0.17 L/min (-0.53 to 0.21) and 0.03 L/min (-0.35 to 0.42), respectively. A heavy AD day was defined as a day with a level of AD particles >0.032 km(-1), which was the average plus one standard deviation during the study period, and six heavy AD days were identified. Change in PEF after a heavy AD day was -0.97 L/min (-1.90 to -0.04). CONCLUSIONS: Heavy exposure to AD particles was significantly associated with decreased pulmonary function in adult asthma patients.

[[CASE OF TUBERCULOSIS COMPLICATIONS DURING PREGNANCY LEADING TO AN INFECTION OUTBREAK].]

A 31-year-old woman developed a constant cough during the 8th week of pregnancy and was diagnosed with bronchial asthma. She was prescribed prednisolone and inhaled corticosteroids. At 28 weeks of pregnancy, she showed worsening weight loss, fever, night sweats, hoarseness, and coughs. At 31 weeks of pregnancy, a scatter shadow and cavitary lesions were detected on the chest radiograph. Acid- fast bacilli smear test and tuberculosis (TB) polymerase chain reaction tests yielded positive results (G-8), and she was diagnosed with TB. Contact tracing and screening indicated 3 patients with TB onset and 18 patients with latent TB infec- tion attributed to the initial patient, who infected a total of 36 people. In the present case, physicians were reluctant to order a chest radiograph for fear of harming the fetus and did not order sputum or interferon gamma release (IGRA) assay tests either. The diagnosis was delayed by 152 days, which was considered as a factor that caused the outbreak. The diag- nosis of TB in a pregnant patient may be very challenging because symptoms may initially be ascribed to the pregnan- cy, and delayed diagnosis and treatment of military TB can lead to the death of the mother and fetus. Consequently, to ensure early diagnosis and treatment, chest radiography and sputum and IGRA tests are recommended for pregnant women who have TB symptoms or are at high risk for TB.

An analysis of etiology, causal pathogens, imaging patterns, and treatment of Japanese patients with bronchiectasis.

BACKGROUND: Bronchiectasis (BE), a syndrome that presents with persistent or recurrent bronchial sepsis related to irreversibly damaged and dilated bronchi, has not been well-characterized in Asians. This study aims to review the etiology, causal pathogens, imaging patterns, and treatment of BE and to define the prognostic factors for acute exacerbation in a Japanese population. METHODS: We performed a retrospective cohort study of 147 patients (104 women; median age, 73 years; range, 30-95 years) with BE at our institution using high-resolution computed tomography to identify imaging patterns and the area of pulmonary involvement. RESULTS: Common BE etiologies were idiopathic (N=50 [34%]), sinobronchial syndrome (N=37 [25%]), non-tuberculous mycobacteriosis (NTM; N=26 [18%]), and previous respiratory infection (N=21[14%]). Pseudomonas aeruginosa was the most common causal pathogen (24%). Common imaging patterns were cylindrical (66%) and mixed including cylindrical pattern (47%). The median number of involved lobes was 2; 49% of the patients had ≥ 3 involved lobes, and 49% had middle lobe and left lingula dominant BE. Patients with predominantly lower lobe BE comprised 4% of the NTM group and 48% of the non-NTM group (P<0.001). In multivariate analysis, cystic BE was a predictor for frequent exacerbations in non-NTM patients (OR=7.947; P=0.004) which led to increased hospital admissions (OR=4.691; P=0.004). CONCLUSIONS: Idiopathic and sinobronchial syndrome were common causes of BE. Etiology did not contribute to imaging pattern or predictors of exacerbations. Cystic BE was a predictor for frequent exacerbations in the non-NTM BE patients.

Pulmonary actinomycosis caused by Actinomyces cardiffensis.

We herein present the first case of pulmonary actinomycosis caused by Actinomyces cardiffensis (A. cardiffensis). A computed tomography (CT) examination revealed a nodule with cavitation in the left upper lobe of the lung. One month later, the lesion had almost disappeared, but a new nodule with peripheral consolidation had appeared in the right middle lobe. Because organizing pneumonia was suspected, prednisolone was begun and improvement was seen. However, two months after the initiation of corticosteroid administration, a chest CT scan showed a lung abscess. The patient underwent surgical resection of the abscess. A. cardiffensis was identified by an amplified 16S ribosomal DNA restriction analysis of a pus sample.

Sarcoid-like reaction in Cryptococcus neoformans infection.

We report a patient with Cryptococcus (C.) neoformans infection, who developed a case of sarcoid-like reaction (SLR). There have been reports of SLRs associated with malignancies. Although differentiating sarcoidosis from SLR is difficult, the patient was diagnosed as SLR because propionibacterium acnes bacterial (PAB) antibody staining of biopsy specimens was negative and the chest radiological findings improved after antifungal treatment. To our knowledge, this is the first report of SLR occurring during cryptococcal infection, and we believe that cryptococcal infection should be considered as a potential cause of SLR.

Multidrug-resistant tuberculosis that required 2 years for diagnosis.

Isoniazid (H) or rifampicin (R) mono-resistant disease can be treated easily and effectively with first-line drugs, while combined H and R resistance (ie, multidrug-resistant tuberculosis (MDRTB)) requires treatment with at least four agents, including a quinolone and an injectable agent. Drug-resistant Mycobacterium tuberculosis strains are reported to be extremely difficult to cultivate invitro. The authors report a case of MDRTB that required 2 years for diagnosis, and was detected only in sputum culture on solid medium. Physicians should consider MDRTB if TB is suspected but pathogens are not detected.

A case of sinobronchial syndrome complicated with myeloperoxidase antineutrophil cytoplasmic antibody associated vasculitis: review of the literature.

We report a case of long-standing sinobronchial syndrome complicated by microscopic polyangiitis (MPA) during the clinical course. The patient showed a mild elevation of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) 17 months prior to the diagnosis of MPA. Subsequently, her MPO-ANCA level gradually became more elevated, and finally her MPO-ANCA level peaked when purpura appeared. Histologic examination of the skin biopsy was consistent with leukocytoclastic vasculitis. Based on the pathological and clinical findings, a diagnosis of MPA was made. Corticosteroid therapy finally led to a remission of MPA with normalized MPO-ANCA titers.

[Clinical analysis of non-tuberculous mycobacteriosis cases complicated with pulmonary aspergillosis].

OBJECTIVES: To clarify the clinical features of nontuberculous mycobacteriosis (NTM) complicated with chronic pulmonary aspergillosis (CPA), we analyzed 257 cases diagnosed with newly developed NTM during the last 12 years in our hospital. RESULTS: Fifty-six per cent of the patients were females. Ten cases (3.9%) of them were complicated with CPA in their clinical course. Mean age at the diagnosis of CPA was 65.5 years, and 8 of 10 cases were males. The average period from the diagnosis of NTM to CPA was almost 7 years. Six NTM cases were classified as the cavitary type and 4 as the nodular-bronchiectasis type. At the time of the diagnosis of CPA, NTM bacilli were isolated in 5 cases, but in the other 5 bacilli were not detected. Radiologically it was found that in many cases the infiltrative shadow had increased and the cavity wall had thickened. Antifungal drug administration was effective in 67% of the cases. In particular, in cases with progressive infiltrative shadows, the antifungal drug was effective in 83% of patients. DISCUSSION: For the clinical management of NTM, careful attention to the complication of CPA is required.

[Pulmonary tuberculosis with atypical radiological findings in a patient with chronic obstructive pulmonary disease].

A 77-year-old-man who had been treated for chronic obstructive pulmonary disease (COPD) was referred to our hospital for further examination of a chest X-ray abnormality. The chest X-ray showed consolidation in the right upper and middle lung field. Chest computed tomography showed an airspace consolidation extending subpleurally and nonsegmentally without nodular lesions. The tentative diagnosis was cryptogenic organizing pneumonia. However, bronchoalveolar lavage fluid was positive for acid-fast bacilli on smear and also positive for tuberculosis PCR, leading to a diagnosis of tuberculous pneumonia. Tuberculous pneumonia in COPD patients can be non-segmental and mimic organizing pneumonia.

[A case of multidrug-resistant tuberculosis who acquired additional resistance to ethambutol before the result of the initial drug sensitivity test was reported].

On December 6, 2008, a 52-year-old man presented to a clinic with chronic cough, sputum, and chest discomfort, which had lasted since mid-November. Since the chest radiograph showed a small cavity with small nodules and granular shadows, he was referred to another hospital. On TB-PCR, the gastric juice was positive. Therefore, on December 16, 2008, treatment for pulmonary tuberculosis was initiated with isoniazid, rifampicin, ethambutol, and pyrazinamide. However, on February 4, 2009, a drug susceptibility test revealed that the bacilli were resistant to isoniazid and rifampicin. Therefore, he was referred to our hospital. At that time, he had no symptoms and his sputum smear was negative. We performed a right upper lobectomy. The smear result of the surgical specimen was heavily positive (equivalent to Gaffky 6), and the drug susceptibility test showed resistance to ethambutol in addition to isoniazid and rifampicin. After surgery, we treated him with pyrazinamide, streptomycin, para-aminosalicylate, ethionamide, and levofloxacin. We report this case of multidrug-resistant tuberculosis without past treatment who acquired additional resistance to ethambutol during the first 2 months of chemotherapy. When treating multidrug-resistant tuberculosis, very careful consideration of susceptibility to other drugs is warranted.

Cough and asthma diagnosis: physicians' diagnosis and treatment of patients complaining of acute, subacute and chronic cough in rural areas of Japan.

BACKGROUND: Cough is one of the most common reasons for visiting a clinic. The causes of cough differ according to the duration of cough. Infectious disease is commonly observed in acute cough while noninfectious disease is commonly observed in chronic cough. On the other hand, cough is frequently observed in patients with asthma/cough variant asthma (CVA). OBJECTIVE: In this study, we investigated the causes of cough in a rural region in Japan and the clinical examination and treatment for the patients diagnosed as asthma/CVA. METHODS: We analyzed 124 patients who complained of cough. RESULTS: The most common reason for acute cough was respiratory tract infection while asthma/CVA is the most common reason for subacute and chronic cough. The diagnostic procedure for asthma/CVA depends on clinical symptoms in asthmatic patients with acute cough. While in asthmatic patients with subacute and chronic cough, diagnosis of asthma depends on clinical examinations including chest radiogram, immunoglobulin E, white blood cells counts, sputum examination or spirometry as well as symptoms. For the treatment of asthma, the use of long-acting beta(2)-stimulant was dominant in asthmatic patients with acute cough while the use of leukotriene receptor and inhaled corticosteroid were dominant in asthmatic patients with subacute or chronic cough. CONCLUSIONS: Diagnosis and treatment for asthma differs according to the duration of cough. Simple guidelines for asthma/CVA according to the duration of cough might be necessary for diagnosis and treatment of asthma/CVA for general physicians especially in rural areas.

[A case of axillary lymph node tuberculosis with paradoxical worsening in breast lesion].

A 80-year-old woman was admitted to our hospital because of left axillary swelling. Needle biopsy specimen showed negative results on a smear for acid-fast bacilli and PCR. The histological findings showed epithelioid cell granuloma with caseous necrosis. QFT TB-2G showed positivity of 1.9 IU/ml in ESAT-6. We diagnosed tuberculous lymphadenopathy and administered antituberculous drugs. After 3 weeks of treatment, in spite of the regression of lymphadenopathy, mammary swelling had progressed. We performed a biopsy of the mammary lesion, but did not detect any abnormal findings. As the mammary lesion had regressed by the continued treatment of antituberculous drugs, we thought the mammary swelling was paradoxical worsening.

[A case of miliary tuberculosis and esophageal perforation secondary to tuberculous mediastinal lymphadenitis].

An 80-year-old woman was admitted to a local hospital following transient disturbance of consciousness after a fall. High intermittent fever developed after hospitalization and she was diagnosed as having mediastinal abscess with esophageal perforation. She underwent mediastinal drainage and surgical repair of the esophagus. Acid-fast bacilli were detected in her sputum. Chest CT scanning showed a diffuse granular shadow. Then she was diagnosed as having miliary tuberculosis and treated with combination of INH, RFP, EB, and PZA. However, five days after treatment was initiated, fever and skin eruption appeared and treatment has to be stopped after one month. Then she was referred to our hospital. We gradually increased the dosages of INH and RFP, which resulted in pyrexia. Therefore, we changed EB to SM. Fever subsided and we were able to administer the full dose of drugs from the beginning of January 2007. Thereafter, the patient improved gradually. However, she died in February 2007. At autopsy, we identified tuberculous mediastinal lymphadenitis, inflammatory granuloma under the esophageal mucosa and miliary tuberculosis. We report this case as a rare case of miliary tuberculosis and esophageal perforation secondary to tuberculous mediastinal lymphadenitis.