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.

[Comparison between pandemic H1N1 2009 influenza pneumonia and seasonal influenza pneumonia in adults].

We compared 126 cases of seasonal influenza pneumonia (seasonal flu) reported between January, 1996 and March, 2009, with 10 cases of laboratory-confirmed pandemic influenza (H1N1) 2009 influenza virus pneumonia (novel flu), based on clinical condition, computed tomography (CT) findings, severity, treatment, and prognosis, to clarify the characteristics of this novel flu. The mean age of subjects was 52.4 years in the novel flu group and 64 years in the seasonal flu group, and novel flu patients were younger than seasonal flu patients. Seasonal flu patients had more underlying diseases than did novel flu patients. The median duration from illness onset to hospitalization was 4 days in both groups. Primary viral pneumonia was present in 70% of novel flu cases and 31% of seasonal flu cases. The proportion of primary virus pneumonia was higher in novel flu patients, and the disease severity of the seasonal flu group was more severe than that of the novel flu group. White blood cell and lymphocyte counts were lower in novel flu patients, and chest CT images showed bilateral shadows and pure ground-glass opacities more frequently in the novel flu cases. There were no differences in treatment, number of days required for the fever to subside, or mortality between the groups.

[A single-center prospective study of viral infection in community-acquired pneumonia in adults].

From July, 2008 to March, 2009, 125 adults with community-acquired pneumonia (CAP) who were admitted to our hospital were retrospectively investigated to elucidate the characteristics of viral infection in adult CAP in Japan. Nasopharyngeal swabs for real-time polymerase chain reaction for 7 types of influenza virus, rhinovirus, respiratory synctial virus, human metapneumovirus, parainfluenza virus, coronavirus, and enterovirus were obtained. Diagnoses of viral infections were established according to positive results in real-time polymerase chain reaction and influenza rapid diagnostic testing, and based on a fourfold increase in antibody titer of influenza virus antibody in paired sera. Overall, a pathogen was identified in 74 patients (59.8%). Of these pathogens, 47 (37.6%) were bacterial, 17 (13.6%) were viral, and 10 (8.0%) were mixed virus and bacterial infection. Influenza virus (n = 12; 9.6%), rhinovirus (n = 8; 6.4%), respiratory syncytial virus (n = 8; 6.4%), and parainfluenza virus (n = 6; 4.8%) were detected. Adenovirus, coronavirus or enterovirus was not detected. Sore throat was more frequently found in patients with viral pneumonia than in those with non-viral pneumonia. Higher age and pneumococcal pneumonia were factors which contributed to severity in the present cases. It is difficult to distinguish viral pneumonia from non-viral pneumonia by clinical findings, and there were few clinically meaningful differences in presentation and severity, and no differences in severity or outcomes according to either the presence or absence of viral infection. Further studies are needed to clarify the possible significance of viral infection in CAP.

[Antisynthetase (anti PL-7 antibody) syndrome presenting as a skin rash and exacerbation of interstitial pneumonia during treatment for rheumatoid arthritis].

A 52-year-old man was admitted to our hospital for progressive dyspnea of 3 months duration and a skin rash of 4 months duration. Previously, he had been given a diagnosis of rheumatoid arthritis at age 40, then a diagnosis of interstitial pneumonia at age 46. Tacrolimus and prednisolone were begun at age 50, and 50 mg/week of etanercept was added 17 months before admission to our hospital. Due to renal dysfunction, tacrolimus was discontinued 9 months before admission. A skin rash developed 4 months before admission, and progressive dyspnea developed over the 3 months before admission. Tacrolimus was restarted at 1 mg/day and prednisolone was increased from 5 mg/day to 15 mg/day; however, neither the skin rash nor the dyspnea improved. After visiting a local physician, the patient was then referred to our institution. On presentation, skin changes such as erythema of the superior palpebrae and fingers were noted. His serum creatine phosphokinase level was elevated, but muscle strength was normal and no abnormal electromyographic and muscle biopsy findings were found. Anti-Jo-1 antibody was negative but anti PL-7 antibody was positive. The patient did not meet the diagnostic criteria of dermatomyositis/ polymyositis, so antisynthetase syndrome was diagnosed. Etanercept was discontinued and the prednisolone increased, which resulted in improvement of the interstitial pneumonia and skin rash. Antisynthetase syndrome should be considered as a differential diagnosis when skin rash and exacerbation of interstitial pneumonia are found during treatment for rheumatoid arthritis.

[Case of bird-related hypersensitivity pneumonitis in a farmer].

A 48-year-old female farmer presented to our hospital with shortness of breath and cough. Her partial pressure of arterial oxygen (PaO2) level on room air was 58.4Torr, and chest computed tomography (CT) showed centrilobular ground-glass micronodules. She was admitted for further evaluation. After admission, symptoms, PaO2, and radiological findings improved without any treatment; however, her symptoms recurred when she returned to work. Exposure to her house did not elicit any symptomatic response. We initially suspected farmer's lung, but inhalation provocation tests with hay showed no significant change in symptoms, laboratory data or radiological findings. Antibody tests for Thermoactinomyces vulgaris or Saccharopolyspora rectivirgula were negative. Because many pigeons were found roosting on her farm, we suspected bird-related hypersensitivity pneumonitis. Precipitating antibodies testing against pigeon serum and IgG and IgA antibodies testing against pigeon dropping extracts were all positive, and bird-related hypersensitivity pneumonitis was diagnosed. Because typically, many birds roost on farms, not only farmer's lung, but also bird-related hypersensitivity pneumonitis, should be included in a differential diagnosis when a farmer clinically suspected to have hypersensitivity pneumonitis is encountered.

[A case of Ehlers-Danlos syndrome suspected from pulmonary hematoma due to disruption of the lung].

A 20-year-old man was referred to our hospital due to hemoptysis. Chest CT showed a ground-glass opacity, suggesting pulmonary bleeding; however, a diagnosis was not obtained. At a follow-up examination after 2 months, Chest CT showed improvement of the ground-glass opacity, however a cavitary nodule had newly appeared. Four months later, another new nodule was found on chest X-ray film. Video-assisted thoracoscopic lung biopsy was performed for pathological diagnosis; disruption of the pleural, lung and blood vessels, and pulmonary hematoma were found. We thought of the fragility of the pleuro-pulmonary connective tissue and also thought of the probability of Ehlers-Danlos syndrome (EDS). A biochemical analysis of cultured dermal fibroblasts and molecular biological examination revealed decreased production of type III collagen in fibroblasts and COL3A1 mutation. We diagnosed this case as vascular EDS. EDS is one of the differential diagnoses in patients presenting hemoptysis and pulmonary hematoma due to disruption of the lung.

[Severe complications and their outcomes in 65 patients with Legionella pneumonia].

The aim of the current study was to investigate the lethal complications of Legionella pneumonia. Severe complications and their outcomes in 65 patients with Legionella pneumonia were studied. All patients who eventually had a fatal outcome or who had severe complications received antimicrobial agents active against Legionella on the admission day. Many patients in the severe complication category had multiple severe complications. Six deaths occurred (mortality rate 9.2%), 4 of which were due to septic shock/multiple organ dysfunction syndrome (MODS) (2 patients) or interstitial pneumonia/pulmonary fibrosis after Legionella pneumonia (2 patients), whereas the other 2 deaths were due to causes unrelated to Legionella pneumonia. Mortality rates for each severe complication were as follows: acute respiratory distress syndrome 27.3% (3 of 11); renal failure 33.3% (2 of 6); disseminated intravascular coagulation 33.3% (2 of 6); severe sepsis 0% (0 of 1); septic shock/MODS 66.7% (2 of 3); interstitial pneumonia/pulmonary fibrosis 50% (2 of 4). Despite prompt diagnosis and appropriate treatment with antimicrobial agents active against Legionella, the lethal complications of Legionella pneumonia are septic shock/MODS and interstitial pneumonia/pulmonary fibrosis.

Ehlers-Danlos syndrome with recurrent spontaneous pneumothoraces and cavitary lesion on chest X-ray as the initial complications.

A 17-year-old-man developed left-sided pneumothorax in 1995. Chest computed tomography (CT) showed a thick-walled cavity in the left lower lobe. Video-assisted thoracic surgery was performed, and pathologic findings of the resected lung showed a cavity, organizing hematoma, and a fibrous nodule. Fragility of connective tissue was suspected, and biochemical and molecular analysis showed reduction of type III collagen production and point mutation of the COL3A1 gene. The patient was diagnosed as having vascular-type Ehlers-Danlos syndrome (EDS). From 2002, the patient developed hemoptysis and bloody sputum once a year. Chest CT detected several nodules and cavities, which were regarded as hematomas with or without excretion. Several vascular changes including aneurysmal formations have been found since 2002, and an aneurysm of the left ulnar artery was resected. The patient continues to be followed regularly on an outpatient basis. We report a rare case of vascular-type EDS who developed pulmonary symptoms as an initial complication.

[Mucoid impaction of the bronchi caused by Schizophyllum commune which developed after discontinuation of itraconazole administration].

We report the case of a 75-year-old woman with mucoid impaction of the bronchi (MIB) due to Schizophyllum commune who improved with itraconazole (ITCZ) administration and relapsed after discontinuation of the drug. She improved again after readministration of ITCZ, and MIB has not recurred. This patient was not suffering from asthma and has been well without steroid administration. Reports of respiratory disorders due to S. commune have been increasing, and cases of allergic bronchopulmonary mycosis (ABPM), fungus ball, lung abscess, and pneumonia have been reported. Including this report, 12 cases of ABPM and MIB due to S. commune have been reported by Japanese authors. Treatment in these 12 cases included anti-fungal agent in 6, single steroid therapy in 3, combination therapy in 2, and bronchial toilet in 1 case. S. commune is not well recognized; however, one should suspect this fungus to be the causative pathogen when Aspergillus species are not detected or anti-Aspergillus antibody is negative.

[Primary ciliary dyskinesia. A case report and comparison with 4 previous cases].

We encountered a 59-year-old man, whose chief complaints were sputum and dyspnea on effort. He had suffered from sinusitis since childhood, and chest computed tomography showed bronchiectasis. Electron microscopic examination of bronchial mucosa biopsied by bronchoscopy showed defect of the inner dynein arm in most of his cilia. We diagnosed primary ciliary dyskinesia. Seminal analysis showed no abnormalities, and the etiology of infertility remains unclear. The present case is the fifth case treated at our hospital. In this paper, we compared this case with 4 cases (2 cases of Kartagener's syndrome and 2 cases of primary ciliary dyskinesia without situs invertus) of our hospital, and findings of previous reports. Primary ciliary dyskinesia should be included in the differential diagnosis even in cases of mild bronchiectasis or normal mobility of sperm. Primary ciliary dyskinesia has more variety in radiological and clinical findings than has been recognized.

[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.

[Case of hot tub lung with confirmation of exacerbation following jet bath use].

A 49-year-old woman presented with exertional dyspnea. Chest CT revealed patchy areas of ground-glass attenuation and ill-defined centrilobular nodules scattered in both lungs. Bronchoalveolar lavage (BAL) fluid showed lymphocytosis. Transbronchial lung biopsy revealed bronchiolocentric alveolitis and well-formed non-necrotizing granulomas were present. She had used a jet bath before the onset of symptoms and mycobacterial culture revealed the presence of Mycobacterium avium complex (MAC) in sputum sample, BAL samples and jet bath water. Restriction fragment length polymorphism (RFLP) analysis revealed that the isolated MAC were essentially clonal. She had used the jet bath for the inhalation provocation study, and after the challenge she complained of dyspnea and have body temperature increased. We diagnosed hot tub lung due to Mycobacterium avium complex. Because avoidance of the jet bath caused improvement of her symptoms and reduced her fever and PaO2 increased by 10 Torr but did not improve the CT findings, antimycobacterial drugs were prescribed. The patient recovered fully. This case proves that the cause of hot tub lung is the use of jet bath through the inhalation provocation study.

[Case of pneumonia caused by beta-lactamase-producing and amoxicillin/clavulanate resistant strains of H. influenzae].

An 80-year-old woman presenting with fever and cough was given a diagnosis of community-acquired pneumonia. She was hospitalized and treated with ampicillin/sulbactam (ABPC/SBT) and clarithromycin (CAM). Gram stain images and sputum culture results led us to believe that the causative agent was Haemophilus influenzae. Drug sensitivity testing indicated that the H. influenzae was a beta-lactamase-positive, ABPC-resistant (BLPAR) strain. Treatment with ABPC/SBT was not clinically effective. We considered the possibility of beta-lactamase-positive amoxicillin/clavulanate-resistant (BLPACR) strains. Further testing revealed that the MIC of ABPC was 128 microg/ml, that of SBT/ABPC was 8 microg/ml, and that of AMPC/CVA was 4 microg/ml. Furthermore, genetic analysis indicated the H. influenzae to be a BLPACR-I strain. The poor clinical course eventually led to a diagnosis of BLPACR. When beta-lactamase-producing H. influenzae is cultured, the possibility of a BLPACR strain resistant to ABPC/SBT and AMPC/CVA must be considered.

[Lung cancer associated with rheumatoid arthritis and usual interstitial pneumonia].

UNLABELLED: To assess the effects of usual interstitial pneumonia (UIP) and smoking in rheumatoid arthritis (RA) patients regarding lung cancer risk, we studied 86 RA patients (14 patients with lung cancer, 58 patients with UIP (RA/ UIP), and 14 patients with both). Among the 28 RA patients with lung cancer, 14 patients (50%) had UIP. Compared to the lung cancer patients without UIP, the proportion of smokers (92.6 vs 50%, p = 0.0328) and total pack-years of smoking (57.1 +/- 37.1 vs 19.5 +/- 21.9, p = 0.003) were significantly higher in lung cancer patients with UIP. There was no significant difference in age, sex, and histological type and location of lung cancer between these two groups. Among the 72 RA/UIP patients, 14 patients (19.4%) had lung cancer. Compared to RA/UIP-only patients, the proportion of smokers (92.6 vs 46.6%, p = 0.002) and total pack-years of smoking (57.1 +/- 37.1 vs 25.4 37.4, p = 0.006) were significantly higher in RA/UIP patients with lung cancer. There was no significant difference in age, sex, and the duration of RA between these two groups. The odds ratio of smoking and total pack-years of smoking over 20 for the development of lung cancer in RA/UIP patients were 14.93 and 21.27, and the differences were statistically significant (p = 0.002 and p < 0.001, respectively). CONCLUSION: 50% of RA patients with lung cancer had RA/UIP and 19.4% of RA/UIP patients had lung cancer. These findings suggest that RA/UIP may be associated with increased risk of development of lung cancer in RA patients. In an RA cohort study to assess the development of lung cancer, RA patients should be divided into two groups, one with RA/UIP and another without RA/UIP. Smokers with RA/UIP should be recommended to cease smoking.

Development of sarcoidosis during etanercept therapy.

This report describes a 65-year-old woman who developed granulomatous lesions consistent with sarcoidosis during etanercept therapy for rheumatoid arthritis. Hilar and mediastinal lymphadenopathy and multiple nodules in both lung fields developed 21 months after administration of etanercept. Noncaseating epithelioid cell granulomas consistent with sarcoidosis were detected in a lung biopsy specimen and in the parietal pleura obtained via thoracotomy. Diseases showing similar histologic changes were excluded, and a diagnosis of sarcoidosis was made. Etanercept was discontinued, which resulted in symptomatic relief, improvement of oxygenation and radiologic findings. There is substantial evidence of tumor necrosis factor-alpha involvement in the induction and maintenance of granuloma formation; however, we should keep in mind that granulomatous disease, such as sarcoidosis, can develop during treatment with a tumor necrosis factor-alpha blocking agent, such as etanercept.

[Long-term CT findings of X-linked agammaglobulinemia with bronchiectasis diagnosed in an adult].

We report a case of X-linked agammaglobulinemia who presented with bronchiectasis. The patient had suffered pneumonia about every five years since childhood until he presented to our hospital at age 34 years old. CT showed bronchiectasis predominantly in the right middle lobe, lingula, and lower lobes. Administration of antibiotics resulted in symptomatic relief. Episodes of recurrent pulmonary infection and bronchiectasis indicated congenital immunodeficiency disorder. Investigation of lymphocyte subsets and serum immunoglobulin values showed remarkable reduction of B cells, IgG 772 mg/dl, IgA 216 mg/dl, and IgM 29 mg/dl. Flow cytometric assessment combined with genetic analysis was performed, and the results showed decreased expression of monocyte Bruton's tyrosine kinase (BTK) and missense mutation of Btk gene. We diagnosed X-linked agammaglobulinemia. IgG remained above 600 mg/dl in this case, we have not administered immunoglobulin after discharge. He suffered from pneumonia in 2004 and 2006 and bronchiectasis has progressed. In this report, we present a case including CT findings over a period of 8 years.

Desquamative interstitial pneumonia with a remarkable increase in the number of BAL eosinophils.

A 57-year old man with desquamative interstitial pneumonia (DIP) showed a marked increase in eosinophils in the bronchoalveolar lavage (BAL) fluid. The patient was referred to our hospital for abnormal shadows on his chest X-ray with no symptoms in May 2007. Computed tomography (CT) showed patchy, peripheral predominate ground-glass opacity. The BAL fluid revealed an increase of the total number of cells, including markedly elevated levels of eosinophils (62.1%), in contrast with only a slight increase of peripheral blood eosinophils, or minimal eosinophils in the alveolar spaces and interstitium of the thoracoscopic lung biopsy specimen. Since the specimens showed findings compatible with a DIP pattern, we diagnosed the patient with DIP. Although it is a rare entity, we should therefore consider DIP in the differential diagnosis when we encounter patients with a marked increase in the number of BAL eosinophils.

[A case of the metastatic calcification of trachea, bronchus, and lung].

A 43-year-old man with chronic renal failure who had been treated by continuous ambulatory peritoneal dialysis (CAPD) was admitted to our hospital because of dry cough. Blood gas analysis showed hypoxemia and metabolic alkalosis. Laboratory data showed elevated levels of phosphorus, BNP, and KL-6. Lung function tests showed restrictive ventilatory failure and impairment of diffusing capacity. Chest CT revealed centrilobular ground-glass opacification in both lung fields, irregular reticular abnormality in left lung field, and calcification around the left shoulder joint. Bronchoscopy revealed a white protruding lesion in the trachea and bronchial membranous portion. Calcified metastasis in the bronchus and lung was confirmed by transbronchial and lung biopsy. Because of no improvement by administration of sevelamer, he started with hemodialysis once a week in addition to CAPD. Cough and bilateral ground-glass opacity were improved.

[Pulmonary infections in patients with rheumatoid arthritis].

We studied 149 rheumatoid arthritis (RA) patients (mean age 68.0 years; 68 men, 81 women) with pulmonary infections. The mean age at the onset of RA and the duration of RA was 57.2 +/- 15.2 years and 10.9 +/- 11.5 years, respectively. Pulmonary infections included nontuberculous mycobacteriosis in 59 patients (Mycobacterium avium complex infection, 50 cases : Mycobacterium kansasii infection, 4 cases; others, 5 cases), pneumonia in 46 patients, pulmonary tuberculosis in 28 patients, pulmonary aspergillosis in 12 patients, pulmonary cryptococcosis in 5 patients, Pneumocystis jiroveci pneumonia in 5 patients, lung abscess in 9 patients, exacerbation of bronchiectasis in 7 patients, and empyema in 4 patients. One hundred percent of patients with exacerbation of bronchiectasis, 91.7% of patients with pulmonary aspergillosis, 87% of patients with pneumonia, and 81.4% of patients with nontuberculous mycobacteriosis had underlying lung diseases. The pulmonary infections during therapy with steroids were pulmonary tuberculosis (78.6%), pneumonia (65.2%), and pulmonary aspergillosis (58.3%), while the pulmonary infections during methotrexate treatment were Pneumocystis jiroveci pneumonia (80%), pulmonary cryptococcosis (40%), and pulmonary tuberculosis (28.6%). Pulmonary infections in RA patients who were taking TNFalpha inhibitors included 1 patient each with nontuberculous mycobacteriosis, pneumonia, pulmonary tuberculosis, and Pneumocystis jiroveci pneumonia. Among the RA patients with lung abscess, malignancy was noted in 55.6%, and diabetes mellitus in 22.2%. Pseudomonas aeruginosa was the second-most-common cause of pneumonia and cause of all exacerbations of bronchiectasis. As well as immunosuppressive medications (steroids, methotrexate, TNFalpha inhibitors) and systemic comorbid diseases, underlying lung diseases could be one of the risk factor for pulmonary infections in patients with RA. The dominant risk factor for each pulmonary infection in patients with RA might be different.

[Pneumocystis carinii pneumonia in a patient with hyper-IgE syndrome].

A 15-year-old girl with abnormal findings detected on a medical check-up chest x-ray film was admitted to our center. High-resolution computed tomography, performed upon hospitalization, demonstrated panlobular nodular darkening in left lung fields, and an expanding, blended, map-like darkening near the pleura. Since a Grocott stain-positive cyst was confirmed histopathologically by transbronchial lung biopsy, the patient was given a diagnosis of Pneumocystis carinii pneumonia. Drug therapy was initiated with sulfamethoxaxole trimethoprim (Baktar), and on the 58th day, chest CT confirmed that the darkening observed at admission had virtually disappeared. Underlying diseases, such as AIDS, malignant lymphoma and secondary immunodeficiency caused by immunosuppressive agents or adrenocorticosteroids, were excluded as the cause of P. carinii pneumonia based on clinical/laboratory findings. Under the suspicion of the possibility of primary immunodeficiency, various immunological competence tests were performed. However, no abnormal findings indicating cell-mediated immunity, humoral immunity, complement immune function, neutrophil phagocytic capacity, or bactericidal capacity were recognized. Since significant increase of serum IgE suggested hyper-IgE syndrome, IgE antibody specific to Staphylococcal enterotoxin A and B, and the exotoxins of Staphylococcus aureus were measured with positive results. Since all three diagnostic criteria for hyper-IgE syndrome (i.e., high serum IgE values, positive IgE antibody specific to Staphylococcal enterotoxin and recurrent infection) were fulfilled, hyper-IgE syndrome was diagnosed. This is a rare case of hyper-IgE syndrome as a result of P. carinii pneumonia.