Radiological and Physiological Predictors of IPF Mortality.

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) has a variable clinical course, which ranges from being asymptomatic to progressive respiratory failure. The purpose of this study was to evaluate the novel clinical parameters of IPF patients who receive an anti-fibrotic agent. Materials and Methods: From January 2011 to January 2021, we identified 39 IPF patients at Okinawa Chubu Hospital. Clinical information was obtained, such as laboratory data, pulmonary function test (PFT) results, and chest images, including of soft tissue thickness and the high-resolution computed tomography (HRCT) pattern at diagnosis. Results: The mean age was 72.9 ± 7.0 (53-85); 27 patients were men and 12 were women. The mean body mass index was 25.1 ± 3.9 (17.3-35). Twenty-four were active smokers and the median number of packs per year was 20. Regarding laboratory findings, mean white blood cell (WBC), lactate dehydrogenase (LDH), and Krebs Von den Lungen-6 (KL-6) values were 7816 ± 1859, 248 ± 47, and 1615 ± 1503, respectively. In PFT, the mean percent predicted FVC, percent predicted total lung capacity, percent predicted functional residual capacity (FRC), and percent predicted diffusion capacity of the lung for carbon monoxide (DLco) were 66.8 ± 14.9%, 71.8 ± 13.7%, 65 ± 39.6%, and 64.6 ± 27.9%, respectively. In chest radiological findings, soft tissue thickness at the right 9th rib was 26.4 ± 8.8 mm. Regarding chest HRCT patterns, 15 showed the definite usual interstitial pneumonia (UIP) pattern, 16 showed the probable UIP pattern, and eight showed the indeterminate for UIP pattern. In the treatment, 24 patients received pirfenidone and 15 patients took nintedanib. The mean observation period was 38.6 ± 30.6 months and 24 patients died. The median survival time was 32.4 months (0.9-142.5). Multivariate analysis adjusted for age showed that both soft tissue thickness [Hazard ratio (HR): 0.912, 95% confidence interval (CI): 0.859-0.979, p-value: 0.009] and percent FRC [HR: 0.980, 95% CI: 0.967-0.992, p-value: 0.002] were robust predictors of IPF mortality. Conclusions: In IPF patients treated with anti-fibrotic agents, both soft tissue thickness at the right 9th rib shown on the chest radiograph and %FRC can be novel predictors of IPF mortality.

Clinical characteristics of dermatomyosits/polymyositis associated interstitial lung disease according to the autoantibody.

BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) often have association with interstitial lung disease (ILD) which have disease specific autoantibody. METHODOLOGY: We reviewed medical records of DM/PM associated ILD from January 2000 to December 2017 according to the autoantibody. RESULT: We identified 52 patients, of whom 30 were antibody negative, 18 had anti aminoacyl-tRNA synthetases (ARS) antibodies and 4 had anti melanoma differentiation-associated gene (MDA)-5 antibody. In high resolution computed tomography (HRCT) of the chest, area of ground glass opacity (GGO), consolidation, and lung tip consolidation were more extensive in anti MDA-5 antibody positive patients (p=0.051, p=0.026, and p=0.027, respectively). Among laboratory findings, GOT had strong correlations with CPK (r=0.889, p < 0.001), and LDH (r=0.910, p < 0.001). Among roentgenographic findings, there were moderate correlations between GGO and consolidation (r=0.668, p < 0.001), and between reticular shadow and traction bronchiectasis (p=0.633, p < 0.001). ILD patients with anti MDA-5 antibodies had decreased survival (1.00 vs 84.3, 22.9 months, p < 0.001). CONCLUSION: ILD patients with anti ARS antibody had intense inflammation, but reversible fibrosis and good prognosis. On the other hand, anti MDA-5 antibody positive ILD patients had shorter survival. Extent of parenchymal shadow and serum GOT were useful indicator of disease activity of PM/DM associated ILD patients in our cohort. J. Med. Invest. 65:251-257, August, 2018.

A 47-Year-Old Man With Progressive Mental Deterioration During Ventilator Management of Asthma in the ICU.

CASE PRESENTATION: A 47-year-old man was admitted to the ICU with acute hypercapnic respiratory failure caused by a severe asthma attack. He had a history of asthma, atrial septal defect, chronic heart failure, and atrial fibrillation. He underwent surgical closure of the atrial septal defect at 7 years of age and was asymptomatic until 38 years of age when he developed congestive heart failure because of structural cardiac abnormalities, including left ventricular systolic dysfunction, biatrial enlargement, and mild mitral and tricuspid regurgitation. After ICU admission, he received ventilator management for asthma, IV prednisone, beta-2 agonist via inhalation, and ceftriaxone. Enteral feeding was provided since the day of admission. Hypercapnia gradually improved over 3 days. He remained alert and could communicate through writing during ventilator management until the third day in the ICU. Enteral feeding was titrated up to 32 kcal/kg/d with 1.6 g/kg/d of protein. Despite the recovery from the initial respiratory failure, he became inactive and lethargic on the fourth day in the ICU. ICU-acquired delirium was suspected, and administration of sedatives and analgesics was discontinued. On the following day, he was unresponsive to stimuli.

Clinical Characteristics Based on the New Criteria of Acute Exacerbation in Patients with Idiopathic Pulmonary Fibrosis.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is the most common parenchymal lung disease. Patients with IPF sometimes develop acute exacerbation (AE), which predicts a poor prognosis. To evaluate the predictors of 90-day mortality of AE in patients with IPF based on the new 2016 criteria. MATERIALS AND METHODS: Sixty-five patients with AE were studied retrospectively between January 2001 and December 2016 at Okinawa Chubu Hospital. RESULTS: The mean age of the patients was 74 years, with 40 (61.5%) men and 25 (38.5%) women. Among our cohort, 37 were current or ex-smokers, with a mean exposure of 32.4 pack-years. The mean grade of the modified Medical Research Council breathlessness scale was 2.8, and the mean duration of dyspnea prior to admission was 6.5 days. Clubbed fingernails were present in 29% of patients. Triggered AE occurred in 12 (18%) of patients. Patients with triggered AE had more extensive ground-glass opacity and higher consolidation scores than the idiopathic AE group (7.3 vs. 4.2, p=0.01). The triggered group had shorter survival than the idiopathic group (1.4 vs. 11.4 months, p=0.094). Serum lactate dehydrogenase (LDH), ΔLDH, and the ratio of partial pressure of oxygen to the fraction of inspiratory oxygen ratio were strong predictors of 90-day mortality. Hazard ratios were 1.003 (p=0.004), 1.004 (p=0.02), and 0.994 (p=0.010), respectively. CONCLUSION: Compared with idiopathic AE, triggered AE in patients with IPF had more extensive infiltration and tended toward shorter survival. Serial trends of serum LDH >2 weeks can help predict prognosis of AE in patients with IPF.

Causative species of nontuberculous mycobacterial lung disease and comparative investigation on clinical features of Mycobacterium abscessus complex disease: A retrospective analysis for two major hospitals in a subtropical region of Japan.

Nontuberculous mycobacteria (NTM) lung disease is increasing globally. Although the etiological epidemiology of NTM is different across regions, Mycobacterium avium complex (MAC) is the leading cause of NTM lung disease in most countries, including mainland Japan. Okinawa is located in the southernmost region of Japan and is the only prefecture categorized as a subtropical region in Japan, it is therefore likely the etiological epidemiology of NTM lung disease is different from mainland Japan. From 2009 to 2015, the medical records of patients, with respiratory specimens positive for NTMs, visiting or admitted to two Okinawan hospitals, were retrospectively analyzed. NTM lung disease cases were defined according to the American Thoracic Society criteria and patient epidemiology and clinical information were evaluated. Results indicate four hundred sixteen patients had bacterial cultures positive for NTM. The most common NTM was M. abscessus complex (MABC) (n = 127; 30.5%), followed by M. intracellulare (n = 85; 20.4%). NTM lung disease was diagnosed in 114 patients. Of these cases, MABC was most common (n = 41; 36.0%), followed by M. intracellulare (n = 31; 27.2%). Chronic obstructive pulmonary disease (COPD) and tracheostomy patients were more likely to develop MABC than MAC lung disease. Multivariate analysis showed a probable association between COPD and MABC lung disease. Chest computed tomography (CT) evaluation revealed bronchiectasis, nodules, and consolidation were less frequently observed in MABC patients compared with MAC patients. Our data suggests Okinawa may be one of the few places where MABC is the predominant pathogen causing NTM lung disease and our results add new insight to MABC lung disease, which is not yet well understood.

Indications of airway stenting for severe central airway obstruction due to advanced cancer.

BACKGROUND: Management of severe central airway obstruction due to advanced cancer is a medical and technical challenge. The impact of airway stenting on the clinical outcome of such patients is unclear. METHOD: This single-center, retrospective study evaluated 21 patients who underwent airway stenting for advanced cancer. We examined predictors of the post-stenting mortality, including age, serum albumin, tracheal diameter, smoking, opioid use, respiratory failure, and performance status (PS). We also compared survival according to the PS. RESULTS: The mean survival period after stenting was 85.2 days. On univariate analysis, age, albumin, PS before airway stenting, respiratory failure, admission route, and PS grade were the candidates as possible predictors of prognosis after the procedure. On multivariate analysis, PS before airway stenting was identified as possible predictor of prognosis after stenting (HR 1.6180, 95% CI 0.969 to 2.7015, p = 0.066). The mean survival period after stenting was significantly longer in the good PS group, compared to the poor PS group (147.8 days vs. 38.2 days,p = 0.0346). CONCLUSION: Airway stenting for advanced cancer may be more effective for patients in good general condition than in those with poor performance status.

Acute Eosinophilic Pneumonia After Resumption of Cigarette Smoking.

Acute eosinophilic pneumonia is a rare entity characterized by rapidly progressive infiltration of eosinophils into the lungs and is often associated with drug exposure or infection. We report a case of a previously healthy 19-year-old woman who presented with acute progressive dyspnea. Chest radiograph revealed diffuse bilateral infiltrates. Based on the results of bronchoalveolar lavage fluid and her clinical course, she was diagnosed as having acute eosinophilic pneumonia. We suspect that the disease was related to smoking because she had started smoking 3 weeks before the onset of symptoms. Given the high prevalence of smoking and initiation of smoking in the military population, it is important for physicians taking care of this population to be aware of this disorder.

Clinical characteristics of idiopathic pulmonary fibrosis patients according to their smoking status.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonias (IIPs) of unknown etiology that often affects male, elderly smokers. However, it is sometimes observed in never smokers. This study aimed to clarify the clinical characteristics of IPF in never-smoking patients compared with those in smoking patients. METHODS: We retrospectively reviewed medical records, pulmonary function tests, and chest high-resolution computed tomography (HRCT) scan of never-smoking and smoking IPF patients from July 1, 2008 to June 30, 2013 at our hospital. RESULTS: We identified 32 never-smoking IPF patients and 66 smoking IPF patients. Never-smoking IPF patients developed more acute exacerbation (AE) than smoking IPF patients (50% vs. 18.2%, P<0.0001). The strongest predictor of AE in never-smoking IPF was modified Medical Research Council (mMRC) breathlessness scale [Hazards ratio (HR), 2.84, P=0.006]. The median survival time of never-smoking and smoking were 18.5 (0.1-138) and 26.3 (0.1-98.4) months, P<0.0001, respectively. The Cox proportional hazard model showed that 1-year mMRC breathlessness scale (HR, 3.24, P=0.001) and gender, age, and physiology (GAP) score (HR, 1.59, P=0.029) were strong predictors of mortality in never-smoking IPF patients at our hospital. CONCLUSIONS: In conclusion, never-smoking IPF patients developed AE more often and showed poor prognosis compared with smoking IPF patients. The 1-year mMRC breathlessness scale was an important predictor of mortality at our hospital.

Body mass index-percent forced vital capacity-respiratory hospitalization: new staging for idiopathic pulmonary fibrosis patients.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is relentless progressive interstitial lung disease. Evaluating predictor of mortality for IPF patients is crucial. The aim of this study was to evaluate the serial trend of important indicators of prognosis and create a useful staging method for IPF patients. METHODS: We retrospectively searched medical records, pulmonary function tests (PFTs), and chest high resolution computed tomography (HRCT) scans from January 1, 2008 through June 30, 2015 at our hospital. We also evaluated the same parameters 1-year later. RESULTS: We identified 65 IPF patients. The mean age was 71.9±1.8 years (range, 22-85 years). In terms of PFTs, mean percent predicted forced vital capacity (%FVC) was 69.8±2.7. Baseline mean body mass index (BMI) was 24.3±0.6 kg/mm2. Mean survival was 39.2 months (range, 0.9-158.9 months). Cox proportional hazard ratios (HRs) showed the following to be predictors of mortality in IPF patients: 1-year BMI (HR: 0.899; 95% CI: 0.825-0.979; P=0.021); 1-year %FVC (HR: 0.932; 95% CI: 0.887-0.979; P=0.005) and 1-year respiratory hospitalization (HR: 3.307; 95% CI: 2.149-5.090; P<0.001). On the basis of these date, we created a new staging method for predicting mortality for IPF patients, consisting of delta BMI, delta %FVC and respiratory hospitalization within a year following diagnosis of IPF (BFR staging). We stratified patients into one of three groups according to the composite points. Mean survival of stages 1, 2, and 3 was 77.9 (30.8-158.9), 43.9 (0.9-145.2) and 14.8 (3.5-32) months (P<0.001), respectively. CONCLUSIONS: In our cohort of IPF patients, this new staging method, including delta BMI and delta %FVC and respiratory hospitalization within 1-year showed a clear survival difference.

Clinical characteristics of idiopathic pulmonary fibrosis patients with gender, age, and physiology staging at Okinawa Chubu Hospital.

BACKGROUND: Gender, age, and physiology (GAP) staging was recently advocated for idiopathic pulmonary fibrosis (IPF). However, clinical findings of GAP staging for IPF are limited. We aimed to investigate the clinical characteristics of IPF patients according to GAP staging in our hospital. METHODS: We retrospectively reviewed patient medical records and chest high-resolution computed tomography (HRCT) images from June 1, 2002, to December 31, 2012. RESULTS: We identified 54 IPF patients with [36 men; mean age: 71 years (range, 53-85 years)]. Mean fibrosis and ground glass opacity (GGO) scores were 1.9 (0-4) and 1.6 (1-3.3), respectively. Mean percent predicted forced vital capacity (% FVC), percent predicted diffusing capacity of the lung for carbon monoxide (% DLco) were 70.6 (6.4-114.3), 49.2 (15-105.9), respectively. Cox proportional hazards model showed that gender, percent predicted diffusing capacity of the lung for carbon monoxide (% DLco), and composite physiologic index (CPI) were strong predictors of mortality. Stage III patients had more pulmonary hypertension (50% vs. 23%, 0%) and progressive modified Medical Research Council (mMRC) changes at 1 year (1.3 vs. 0.6, 1.1; P=0.07) compared with other stages. CONCLUSIONS: In our cohort, GAP staging was useful for evaluating IPF severity. Stage III patients might had more pulmonary hypertension and progressive dyspnea. Multicenter analyses are warranted to confirm these findings.

Validation of sputum Gram stain for treatment of community-acquired pneumonia and healthcare-associated pneumonia: a prospective observational study.

BACKGROUND: The usefulness of sputum Gram stain in patients with community-acquired pneumonia (CAP) is controversial. There has been no study to evaluate the diagnostic value of this method in patients with healthcare-associated pneumonia (HCAP). The purpose of this study was to evaluate the usefulness of sputum Gram stain in etiological diagnosis and pathogen-targeted antibiotic treatment of CAP and HCAP. METHODS: We conducted a prospective observational study on hospitalized patients with pneumonia admitted to our hospital from August 2010 to July 2012. Before administering antibiotics on admission, Gram stain was performed and examined by trained physicians immediately after sputum samples were obtained. We analyzed the quality of sputum samples and the diagnostic performance of Gram stain. We also compared pathogen-targeted antibiotic treatment guided by sputum Gram stain with empirical treatment. RESULTS: Of 670 patients with pneumonia, 328 were CAP and 342 were HCAP. Sputum samples were obtained from 591 patients, of these 478 samples were good quality. The sensitivity and specificity of sputum Gram stain were 62.5% and 91.5% for Streptococcus pneumoniae, 60.9% and 95.1% for Haemophilus influenzae, 68.2% and 96.1% for Moraxella catarrhalis, 39.5% and 98.2% for Klebsiella pneumoniae, 22.2% and 99.8% for Pseudomonas aeruginosa, 9.1% and 100% for Staphylococcus aureus. The diagnostic yield decreased in patients who had received antibiotics or patients with suspected aspiration pneumonia. Pathogen-targeted treatment provided similar efficacy with a decrease in adverse events compared to empirical treatment. CONCLUSIONS: Sputum Gram stain is highly specific for the etiologic diagnosis and useful in guiding pathogen-targeted antibiotic treatment of CAP and HCAP.

Staging of acute exacerbation in patients with idiopathic pulmonary fibrosis.

BACKGROUND: The purpose of this study was to evaluate the predictors of a 3-month mortality rate of acute exacerbation of idiopathic pulmonary fibrosis (IPF) and provide a new staging system. METHODS: A total of 594 patients with IPF were included in this retrospective, observational study conducted from January 2001 to December 2010 at Okinawa Chubu Hospital. RESULTS: Among the 594 patients, 58 (9.8 %) developed acute exacerbation (AE) of IPF during the 10-year observation period. The median follow-up period for AE was 10.4 months. In-hospital mortality was 56.9 % and the 3-month mortality rate was 63.8 %. We identified the following four parameters in a multivariate analysis as: serum lactate dehydrogenase, sialylated carbohydrate antigen (KL-6), ratio of partial pressure of oxygen and fraction of inspiratory oxygen, and total extent of abnormal findings on high-resolution computed tomography of the chest. Patients were divided into two groups on the basis of the four composite parameters. Patients in the extensive disease-stage group required more mechanical ventilation and intensive therapy than those in the limited disease-stage group. The 3-month mortality rate was higher in patients in the extensive disease-stage group than in patients in the limited disease-stage group (80.6 vs. 54.5 %, respectively; p = 0.007). CONCLUSIONS: Staging of AE in patients with IPF provided useful information regarding disease severity and short-term outcome.

A prospective comparison of nursing- and healthcare-associated pneumonia (NHCAP) with community-acquired pneumonia (CAP).

Nursing- and healthcare-associated pneumonia (NHCAP) has been proposed by the Japanese Respiratory Society as a new category of pneumonia considering the characteristics of the Japanese medical care environment. It is necessary to ascertain the epidemiology and clinical outcomes of NHCAP. A prospective study was conducted of patients with pneumonia who were hospitalized at our hospital from August 2011 to July 2012. We compared 192 cases of NHCAP with 114 cases of community-acquired pneumonia (CAP). Compared with CAP, NHCAP had a higher disease severity, higher 30-day mortality rate (10.9 vs. 3.5 %, P = 0.022), and longer length of hospital stay (median, 12 vs. 8 days, P < 0.001). Streptococcus pneumoniae was the most frequent causative pathogen in both NHCAP and CAP (33.9 vs. 34.8 %, P = 0.896). The incidence of atypical pathogens in NHCAP was low (1.7 %). Multidrug-resistant (MDR) pathogens were isolated more frequently in NHCAP than in CAP, but there was no significant difference (11.0 vs. 4.5 %, P = 0.135). Among 192 NHCAP patients, 122 (63.5 %) were aspiration pneumonia. Aspiration pneumonia was associated with poor outcomes and was considered a major characteristic of NHCAP. Our study suggested that many patients with NHCAP do not need broad-spectrum antibiotic therapy targeting MDR pathogens. Excess mortality in NHCAP patients is the result of patient backgrounds or disease severity rather than the presence of MDR pathogens.

A cohort study of mortality predictors and characteristics of patients with combined pulmonary fibrosis and emphysema.

OBJECTIVES: Our purpose was to assess the clinical data, predictors of mortality and acute exacerbation (AE) in combined pulmonary fibrosis and emphysema (CPFE) patients. DESIGN: Single-centre retrospective cohort study. SETTING: Teaching hospital in Japan. PARTICIPANTS: We identified 93 CPFE patients with high-resolution computed tomographic (HRCT) through multidisciplinary discussion. Patients who had connective tissue disease, drug-associated interstitial lung disease and occupationally related interstitial lung disease, such as asbestosis and silicosis, were excluded. INTERVENTIONS: There were no interventions. METHODS: Medical records and HRCT scans from January 2002 through December 2007 were reviewed retrospectively at our hospital. Ninety-three patients had CPFE. RESULTS: The mean age of CPFE patients was 74 years. Idiopathic pulmonary fibrosis and non-specific interstitial pneumonia were observed as distinct HRCT patterns. Forty-two patients showed finger clubbing. Mean serum Krebs von den Lungen-6 (KL-6) and per cent predicted forced vital capacity (%FVC) were 1089 IU/l, 63.86%, respectively. Twenty-two patients developed AE during observation period. Baseline KL-6 was a strong predictor of AE (OR=1.0016, p=0.009). Finger clubbing (HR=2.2620, p=0.015) and per cent predicted forced expiratory volume in one second/%FVC more than 1.2 (HR=1.9259, p=0.048) were independent predictors of mortality in CPFE. CONCLUSIONS: Baseline serum KL-6 was a useful predictor of AE (cut-off =1050, receiver operator characteristic curve: 0.7720), which occurred in 24% (22/93) of the CPFE patients. Finger clubbing and per cent predicted forced expiratory volume in one second/%FVC more than 1.2 were independent predictors of mortality.

Elsberg syndrome with eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis.

A 42-year-old man was admitted to our hospital with a history of fever, headache and disorientation. His cerebrospinal fluid revealed eosinophilia and his serum had an antibody against Angiostrongylus cantonensis (A. cantonensis). Then, he was diagnosed as eosinophilic meningoencephalitis caused by A. cantonensis. He was treated with repeated lumbar punctures and oral prednisolone. Although a symptom he had been suffering from at the time of his admission was urinary retention, this symptom disappeared as his general condition improved. Therefore his case was considered to be Elsberg syndrome with eosinophilic meningoencephalitis caused by A. cantonensis.