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.

Incidence and etiology of chronic pulmonary infections in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The incidence and etiologies of chronic pulmonary infection (CPI) in patients with idiopathic pulmonary fibrosis (IPF) have been poorly investigated. METHODS: We conducted a retrospective study of 659 patients with IPF to assess the incidence, etiologies, and risk factors of CPI development. CPI was defined if the etiology of infection was diagnosed one or more months after the onset of symptoms or upon the appearance of new shadows on pulmonary radiological images. RESULTS: At IPF diagnosis, 36 (5.5%) patients had CPI, and 46 (7.0%) patients without CPI at IPF diagnosis developed CPI over a median follow-up period of 6.1 years. The incidence density of CPI development was 18.90 cases per 1000 person-years. Detected organisms from these 46 patients were Mycobacterium avium complex in 20 patients, other nontuberculous mycobacteria in 4, M. tuberculosis in 7, Aspergillus spp. in 22, and Nocardia sp. in one. In a multivariate Cox regression hazard model, PaO2 <70 Torr and KL-6 ≥2000 U/mL were associated with CPI development. CONCLUSIONS: Nontuberculous mycobacteria, M. tuberculosis, and Aspergillus and Nocardia spp. were the four most frequent etiologies of CPI in patients with IPF. During follow-up of IPF, clinicians should pay attention to the development of CPI, especially in patients with PaO2 <70 Torr or KL-6 ≥2000 U/mL.

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

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

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.

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

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

Smoking history and emphysema in asthma-COPD overlap.

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

Clinical and Radiographic Comparison of Influenza Virus-associated Pneumonia among Three Viral Subtypes.

OBJECTIVE: Presently, the predominant subtypes of influenza viruses in the world, except for those in local epidemics, include influenza pandemic H1N1 2009 (pH1N1), H3N2, and B viruses. There are few reports on the differences in the clinical features, radiographic findings, treatment, and outcomes of influenza virus-associated pneumonia among these three viral subtypes. The purpose of this study was to investigate whether the clinical features, radiographic findings, treatment, and outcomes differ among the viral subtypes. METHODS: We retrospectively analyzed 96 patients with influenza virus-associated pneumonia whose viral subtypes were clarified. RESULTS: Patients with pH1N1 virus-associated pneumonia tended to be young. The frequency of primary viral pneumonia differed among the virus-associated pneumonia subtypes (pH1N1, 80%; H3N2, 26.5%; and B, 31%). Patients with pH1N1 virus-associated pneumonia more frequently showed bilateral ground-glass opacities (GGOs), which affected more lobes than in patients with H3N2 and B virus-associated pneumonia. However, patients with H3N2 virus-associated pneumonia showed a higher frequency of consolidation and diffuse bronchial wall thickening than did the patients with pH1N1 virus-associated pneumonia. The severity and mortality did not differ among the three pneumonia subtypes. CONCLUSION: In the patients who developed influenza virus-associated pneumonia, those with pH1N1 virus-associated pneumonia frequently developed primary viral pneumonia resulting in bilateral and broad areas of GGOs on imaging, whereas patients with H3N2 virus-associated pneumonia frequently showed consolidation and diffuse bronchial wall thickening on pulmonary imaging.

Multicenter study of quantitative computed tomography analysis using a computer-aided three-dimensional system in patients with idiopathic pulmonary fibrosis.

PURPOSE: To evaluate the feasibility of automated quantitative analysis with a three-dimensional (3D) computer-aided system (i.e., Gaussian histogram normalized correlation, GHNC) of computed tomography (CT) images from different scanners. MATERIALS AND METHODS: Each institution's review board approved the research protocol. Informed patient consent was not required. The participants in this multicenter prospective study were 80 patients (65 men, 15 women) with idiopathic pulmonary fibrosis. Their mean age was 70.6 years. Computed tomography (CT) images were obtained by four different scanners set at different exposures. We measured the extent of fibrosis using GHNC, and used Pearson's correlation analysis, Bland-Altman plots, and kappa analysis to directly compare the GHNC results with manual scoring by radiologists. Multiple linear regression analysis was performed to determine the association between the CT data and forced vital capacity (FVC). RESULTS: For each scanner, the extent of fibrosis as determined by GHNC was significantly correlated with the radiologists' score. In multivariate analysis, the extent of fibrosis as determined by GHNC was significantly correlated with FVC (p < 0.001). There was no significant difference between the results obtained using different CT scanners. CONCLUSION: Gaussian histogram normalized correlation was feasible, irrespective of the type of CT scanner used.

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 Pneumonia and the Effect of the Pneumococcal Vaccine in Patients With Chronic Airflow Obstruction.

Background: To evaluate the risk factors for pneumonia and the efficacy of the pneumococcal polysaccharide vaccine (PPV) in patients with chronic airflow obstruction. Methods: We retrospectively studied the risk factors for pneumonia in 820 consecutive patients with chronic obstructive pulmonary disease (COPD) (n=509) and patients with asthma-COPD overlap syndrome (ACOS) (n=311). The effects of asthma, age, smoking history, chronic sputum, use of inhaled corticosteroids, percent predicted forced vital capacity (%FVC), percent predicted forced expiratory volume in 1 second (%FEV1), body mass index (BMI), computed tomography (CT)-diagnosed emphysema, and the pneumococcal vaccination on the frequency of pneumonia were assessed. Results: There was no difference in the frequency of pneumonia in patients with COPD and those with ACOS. In a univariate analysis, age (p= 0.031), %FVC (p< 0.001), %FEV1 (p < 0.001), BMI (p = 0.003), the presence of emphysema (p < 0.001) and a history of vaccination with the PPV (p = 0.034) were associated with the frequency of pneumonia. A multivariate analysis identified low BMI, the presence of emphysema and the absence of a pneumococcal vaccination as independent risk factors. The combination index of these factors, the BOVE index, which is calculated from low BMI (<22 kg/m2), low %FEV1 (<60%), vaccination history and emphysema was associated with the overall frequency of pneumonia. Conclusions:The index of multidimensional risk factors is useful to predict the frequency of pneumonia in patients with chronic airflow obstruction. The pneumococcal vaccination was associated with significantly lower incidence of pneumonia.

Etiology and Outcome of Diffuse Acute Infectious Bronchiolitis in Adults.

RATIONALE: The etiology and outcome of diffuse acute infectious bronchiolitis (DAIB) in adults is not well known. OBJECTIVES: To retrospectively review adult patients with DAIB without pneumonia, document the etiologies and outcomes, and assess the relation between DAIB and postinfectious bronchiolitis obliterans. METHODS: We retrospectively analyzed medical records of 1,664 patients with lower respiratory tract infections admitted to our institution in Saitama, Japan. DAIB was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated mainly multiple centrilobular nodules in four or more lobes. Pneumonia was diagnosed when patients developed acute feverish lower respiratory tract infection and chest computed tomography demonstrated consolidation and/or ground-glass opacities with or without centrilobular nodules. MEASUREMENTS AND MAIN RESULTS: Of the 1,664 patients, 20 (1.2%) and 1,644 (98.8%) patients were diagnosed as having DAIB and pneumonia, respectively. Of the 20 patients with DAIB, the etiology was determined in 16 (80%): 13 (65.0%) had a single pathogen and 3 (15.0%) had two pathogens. Detected organisms included Mycoplasma pneumoniae in eight (40.0%) patients, influenza virus in two (10.0%), influenza virus and Streptococcus pneumoniae in two (10.0%), Haemophilus influenzae in three (15.0%), and respiratory syncytial virus and rhinovirus in one (5.0%) patient. All patients improved and none developed postinfectious bronchiolitis obliterans. CONCLUSIONS: The three most common etiologies of DAIB in the studied adults were M. pneumoniae, influenza virus, and H. influenzae. None of the patients with DAIB developed postinfectious bronchiolitis obliterans.

Retrospective study of the predictors of mortality and radiographic deterioration in 782 patients with nodular/bronchiectatic Mycobacterium avium complex lung disease.

OBJECTIVES: Some patients with nodular/bronchiectatic Mycobacterium avium complex lung disease (NB MAC-LD) deteriorate and die. The main aim of the study is to evaluate the prognostic factors and radiographic outcomes in patients with NB MAC-LD. SETTING: Retrospective single-centre review. PARTICIPANTS: 782 HIV-negative patients with NB MAC-LD treated at our institution in Japan. PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause and MAC-LD progression mortality rates and the prognostic factors, and radiographic deterioration rates and the prognostic factors. RESULTS: Mean age was 68.1 years, and median follow-up period was 4.3 years. Death from any cause and progression of MAC lung disease (MAC-LD) occurred in 130 (16.6%), and 19 (2.4%) patients, respectively. All-cause and MAC-LD progression 10-year mortality rates were 27.4% and 4.8%, respectively. In 536 patients with MAC-LD who were followed-up for more than 1 year, radiographic deterioration occurred in 221 (41.2%) patients and median time-to-radiographic deterioration was 9 years. A multivariate Cox proportional hazard model showed male sex, older age, body mass index <18.5 kg/m(2), absence of bloody sputum, hypoalbuminaemia and erythrocyte sedimentation rate >40 mm/h to be negative prognostic factors for all-cause mortality, and the presence of idiopathic pulmonary fibrosis, haemoglobin <11.3 mg/dL, C reactive protein >1.0 mg/dL and the presence of cavity to be negative prognostic factors for radiographic deterioration. CONCLUSIONS: Only 2.4% of patients with NB MAC-LD died from MAC-LD progression. As clinical trials testing the effectiveness of drug therapy in patients with NB MAC-LD are being designed and implemented, the primary end point could be time-to-radiographic deterioration, and trial patients need to be stratified according to these prognostic factors before randomisation.

Lobe-based computed tomography assessment of airway diameter, airway or vessel number, and emphysema extent in relation to the clinical outcomes of COPD.

OBJECTIVE: The aim of this study was to evaluate the relationship between computed tomography assessed lobe-based lung parameters and the clinical outcomes of patients with chronic obstructive pulmonary disease (COPD), including the frequency of exacerbation and annual change in forced expiratory volume in 1 second (FEV1). PATIENTS AND METHODS: We studied 65 patients with COPD. We reconstructed computed tomography images to trace the bronchial tree from right B1 to B10 and created 3 cm circle images around the airways exactly perpendicular to the airway axis in the central, middle, and peripheral zones of the bronchi. The number of airways and vessels, airway inner diameter and area of emphysema in the circles were calculated for each segment. Then, we analyzed the relationships between the lobe-based image parameters and the frequency of exacerbation and annual decline in the FEV1. In addition, we assessed the effects of proximal airway lumen-obliterated emphysema (ALOE) on these clinical features. RESULTS: The airway diameter was not associated with the frequency of exacerbation or annual decline in FEV1. Among the structural parameters, lower lobe emphysema was most associated with the frequency of exacerbation. The reductions in the number of airways and vessels in total lobe were associated with the annual decline in FEV1. The subgroup of patients with ALOE demonstrated lower FEV1 and more frequent exacerbation than those without ALOE. CONCLUSION: Lower lobe emphysema predicts frequent COPD exacerbation, whereas the annual decline in FEV1 is associated with the number of airways and vessels in total lobe.

Multiple, thin-walled cysts are one of the HRCT features of airspace enlargement with fibrosis.

PURPOSE: Airspace enlargement with fibrosis (AEF) has been identified pathologically as a smoking related change. We sought to identify the HRCT findings of AEF and search for distinguishing features from honeycombing. MATERIALS AND METHODS: 50 patients (47 males; mean age 69) were evaluated. All had undergone lobectomy for lung cancer and had confirmed AEF and/or usual interstitial pneumonia (UIP) by pathological evaluation. HRCT findings were first evaluated preresection for resected lobes, and then correlated with the subsequent pathological findings in the resection specimens. Three groups were devised: one with AEF alone to determine the HRCT findings of AEF, a second with AEF and UIP and third with UIP alone. HRCT features of AEF and honeycombing were compared. RESULTS: There were 11 patients (10 male; mean age 69) with AEF alone, 24 patients (22 male; mean age 69) with AEF and UIP, and 15 patients (15 male; mean age 68) with UIP alone. The HRCT on the AEF alone showed subpleural (but not abutting the pleura) multiple thin-walled cysts (MTWCs) in 7 and reticular opacities in 3. The HRCT in AEF and UIP showed MTWCs in 10, reticular opacities in 17; and honeycombing in 5. Among these 35 patients with the pathological finding of AEF (with or without UIP), 17 showed MTWCs. The maximum cyst wall thickness of MTWCs (mean 0.81 mm) was significantly thinner than that of honeycombing (mean 1.56 mm). MTWCs did not locate in lung base and was distant from the pleura. HRCT findings correlated with gross findings on both cysts and honeycombing. No MTWCs were seen in the 15 patients with UIP, 8 of 15 had honeycombing on CT. CONCLUSIONS: We confirmed that HRCT features of AEF were MTWCs and/or reticular opacities. MTWCs might be distinguished from those of honeycomb change. While we prefer the term MTWCs, these sorts of changes have probably been confused with/interpreted as honeycombing and/or empysema in the past.

Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Increasing evidence indicates that antineutrophil cytoplasmic antibody (ANCA)-positive conversion occurs in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) and as a result, some of these patients develop microscopic polyangiitis (MPA). However, the incidence density of these patients is not well known. OBJECTIVES: To explore the incidence of ANCA-positive conversion and development of MPA during the disease course in patients with IPF and to evaluate whether corticosteroid therapy reduces MPA development in patients with IPF with myeloperoxidase (MPO)-ANCA positivity at diagnosis or who later acquire MPO-ANCA positivity. METHODS: We retrospectively analysed the medical records of 504 Asian patients with IPF treated at our institution in Saitama, Japan. RESULTS: Of the 504 patients with IPF, 20 (4.0%) had MPO-ANCA and 16 (3.2%) had PR-3-ANCA when first evaluated. In 264 of 504 patients with IPF, ANCA was measured repeatedly and seroconversion to MPO-ANCA and PR3-ANCA occurred in 15 (5.7%) and 14 (5.3%) patients, respectively, and 9 of 35 patients who were either MPO-ANCA positive at IPF diagnosis or who subsequently seroconverted developed MPA. None of the nine patients who developed MPA had been previously treated with steroids. The incidence of MPA tended to be lower in patients treated than not treated with corticosteroids although this was not statistically significant. CONCLUSIONS: Some patients with IPF with MPO-ANCA positivity at IPF diagnosis or with MPO-ANCA-positive conversion during follow-up developed MPA. Clinical trials to determine whether corticosteroid therapy can reduce MPA development and prolong survival in MPO-ANCA-positive patients with IPF should be considered.

CT analysis of the effect of pirfenidone in patients with idiopathic pulmonary fibrosis.

PURPOSE: Pirfenidone is a new, anti-fibrotic drug used for the treatment of idiopathic pulmonary fibrosis (IPF). The aim of this study was to evaluate the utility of computed tomography (CT) in the imaging assessment of the response to pirfenidone therapy. MATERIALS AND METHODS: Subjects were 78 patients with IPF who underwent CT on two occasions with one-year interval (38 consecutive patients treated with pirfenidone and 40 age-matched control). Changes in the fibrous lesion on sequential CTs were assessed as visual score by two radiologists. We measured the volume and change per year of fibrous pattern (F-pattern) quantitatively using a computer-aided system on sequential CTs. RESULTS: The baseline vital capacity (%pred VC) was 74.0 ± 14.0% in the pirfenidone group and 74.6 ± 16.6% in controls (p=NS). Deterioration of respiratory status was defined as 10% or greater decline in %pred VC value after 12-month treatment. A significantly larger proportion of pirfenidone-treated patients showed stable respiratory status (21 of 38, 65.6%) than the control (15 of 40, 37.5%). The change in fibrous lesion was significantly smaller in the pirfenidone group than the control in both of visual score (p=0.006) and computer analysis (p<0.001). The decline in VC correlated significantly with the increase in fibrotic lesion (p<0.001). CONCLUSION: CT can be used to assess pirfenidone-induced slowing of progression of pulmonary fibrosis.

CT-diagnosed emphysema and prognosis of chronic airflow obstruction: a retrospective study.

OBJECTIVE: CT-diagnosed emphysema is associated with poor prognosis in chronic obstructive pulmonary disease (COPD). Its clinical impacts on prognoses of asthma with chronic airflow obstruction (CAO) are not well known. We sought to compare mortalities and prognostic factors in COPD and asthma with CAO by the presence or absence of CT-diagnosed emphysema. DESIGN: Retrospective cohort study. SETTING: Referral centre hospital for respiratory disease. PARTICIPANTS: 1272 patients aged over 40 years with CAO (January 2000 to December 2011). CAO was defined as a forced expiratory volume in 1 s/forced vital capacity <0.7 after bronchodilator use throughout the observation period. PRIMARY AND SECONDARY OUTCOME MEASUREMENTS: Overall mortality served as the primary endpoint. We compared mortalities and prognostic factors of COPD and asthma subgroups with or without emphysema. Secondary endpoints were the prevalence of COPD and asthma in patients with CAO. RESULTS: Overall, diagnoses included COPD with emphysema in 517 (40.6%) patients, COPD without emphysema in 104 (8.2%) patients, asthma with emphysema in 178 (13.9%) patients, asthma without emphysema in 169 (13.3%) patients, other respiratory diseases (RD) with emphysema in 128 (10.1%) patients, and other RD without emphysema in 176 (13.8%) patients. Patients with asthma without emphysema had the best prognosis followed by those with asthma with emphysema, COPD without emphysema and COPD with emphysema. Each subgroup had distinct prognostic factors. Presence of emphysema was an independent risk factor for de novo lung cancer among patients with CAO. CONCLUSIONS: Patients with asthma with CAO have a better prognosis than patients with COPD. The presence of CT-diagnosed emphysema predicts poor prognosis in COPD and asthma with CAO.

Clinical investigation of nontuberculous mycobacterial lung disease in Japanese patients with rheumatoid arthritis receiving biologic therapy.

OBJECTIVE: To review patients with rheumatoid arthritis (RA) receiving biologic therapy following a diagnosis of nontuberculous mycobacterial (NTM) lung disease and to evaluate disease deterioration according to clinical and radiological features and anti-NTM therapy. METHODS: We retrospectively analyzed medical records of 11 human immunodeficiency virus-negative patients with RA (median age, 64 years) receiving biologic therapy following diagnosis of NTM lung disease. RESULTS: NTM species included Mycobacterium avium complex in 9 patients (81.8%) and M. gordonae in 2 (18.2%). Underlying respiratory disease was present in 6 patients (54.5%), and most (81.8%) had radiographic features of nodular/bronchiectatic disease. Extent of NTM disease was 1-2 pulmonary lobes in 6 patients (54.5%), 3-4 lobes in 5 patients (45.5%), and 5-6 lobes in none. The results of radiological evaluations were unchanged or improved in 7 patients (63.6%) and worsened in 4 (36.4%). Radiological outcome was worse in patients with poor RA control despite their receiving biologic therapies for RA. Two of 3 patients receiving anti-NTM therapy as initial management for NTM improved, and 1 worsened. Three of 4 patients with worsened radiological outcome had high erythrocyte sedimentation rate (> 50 mm/h). CONCLUSION: Radiological deterioration was not observed in the majority of patients with RA receiving biologic therapy with NTM lung disease, and radiological outcome of pulmonary NTM was favorable in some patients undergoing anti-NTM therapy. Further studies focusing on disease deterioration according to biologic therapy received during NTM followup are warranted to determine appropriate treatment of RA patients with NTM lung disease.

Changes in the airway lumen and surrounding parenchyma in chronic obstructive pulmonary disease.

BACKGROUND: The purpose of this study was to examine changes in the airway lumen and parenchyma in relation to lung function in patients with chronic obstructive pulmonary disease (COPD) compared with controls. METHODS: We studied 70 patients with COPD and 15 normal subjects. Using reconstructed computed tomography (CT) images, we traced the bronchial trees and reconstructed 3 cm circle images around the airways exactly perpendicular to the airway axis at the peripheral, middle, and central zones of the bronchi. We measured the number of airways and vessels, the airway inner diameter, and the area of emphysema in the circles, and analyzed the relationship of these image parameters to lung function. RESULTS: Reduced airway numbers and increased upper lobe emphysema were observed even in early spirometric stages in patients with COPD compared with controls. Other findings included decreased airway inner diameter in advanced spirometric stages. The numbers of peripheral zone bronchi, the extent of the middle zone emphysematous area, and the mean airway inner diameter of the airways were the best predictors of spirometric parameters. A portion of the airways in patients with COPD showed a loss of airway patency at middle or central zone bronchi predominantly in the late spirometric stages. Lumen-obliterated bronchial trees could be traced into emphysematous areas showing air trapping. CONCLUSION: Compared with controls, our CT observations in patients with COPD showed that airway lumen and lung parenchyma changes along airways differed by spirometric stage, and these changes were associated with decreased lung function. A portion of CT-identified emphysema in patients with COPD appeared to be due to lumen-obliterated airways in the bronchial tree.

Prognostic factors and radiographic outcomes of nontuberculous mycobacterial lung disease in rheumatoid arthritis.

OBJECTIVE: The aims of our study were to retrospectively review patients with rheumatoid arthritis (RA) with nontuberculous mycobacterial (NTM) lung disease, to assess the prognostic factors, and to analyze the time to disease deterioration according to the antirheumatic drugs received during the NTM lung disease followup period. METHODS: We retrospectively analyzed medical records of 98 HIV-negative RA patients with NTM lung disease treated at our institution, and investigated potential risk factors of mortality with Cox regression analysis. Time to radiologic deterioration was evaluated if antirheumatic drugs were not changed during observational periods and computed tomography was performed once each year. RESULTS: Mean patient age was 67.6 years, and median followup period was 4.4 years. NTM species included Mycobacterium avium complex (83.7%), M. kansasii (6.1%), M. gordonae (6.1%), and others (4.1%). Radiographic features included nodular/bronchiectatic (NB) disease (57.1%), fibrocavitary (FC) disease (14.3%), FC+NB disease (16.3%), and other types (12.2%). Initial management included observation in 74 (75.5%) patients. Negative prognostic factors of mortality were C-reactive protein (CRP) ≥ 1.0 mg/dl and radiographic features of FC, FC+NB, or other disease types. Median time to radiologic deterioration was 3.6 years. Erythrocyte sedimentation rate (ESR) > 50 mm/h was a negative prognostic factor of radiologic deterioration. CONCLUSION: The most frequent NTM species was M. avium complex. CRP and radiographic features were prognostic factors for all-cause mortality, and ESR was a prognostic factor of radiologic deterioration. Further studies are warranted focusing on time to disease deterioration according to antirheumatic drug received during NTM followup.