Is Metalloproteinase-7 Specific for Idiopathic Pulmonary Fibrosis?

BACKGROUND: Matrix metalloproteinase (MMP)-7 was reported to be a key molecule in the pathogenesis of idiopathic pulmonary fibrosis (IPF) based on the result of microarray analysis and knockout mice. However, the role of MMP-7 has not been determined in other types of idiopathic interstitial pneumonia (IIP). The aim of this study was to investigate the role of MMP-7 in IIP by comparing its expression in usual interstitial pneumonia (UIP) and cryptogenic organizing pneumonia (COP). METHODS: Levels of MMP and tissue inhibitors of metalloproteinase in BAL fluid and their expression on lung tissues were compared between normal control subjects (n = 5) and the patients with IPF (n = 6) and COP (n = 11). RESULTS: There was no significant difference in BAL fluid MMP-7 levels between UIP and COP, although it was higher in both diseases compared to normal control subjects. Furthermore, the pattern and the degree of MMP-7 expression in lung tissues were also similar in both IPF and COP, whereas MMP-2 level was higher in COP and MMP-9 level was higher in IPF. CONCLUSION: MMP-7 seems to play an important role in the pathogenesis of not only IPF but also COP; therefore, it may not be the key factor determining the prognosis or reversibility of IIPs.     

Outcomes and safety of surgical lung biopsy for interstitial lung disease

STUDY OBJECTIVES: To determine the safety of surgical lung biopsy (SLB) in patients with interstitial lung disease (ILD), and specifically in those with idiopathic pulmonary fibrosis (IPF). DESIGN: Retrospective cohort. SETTING: Tertiary care university-affiliated military medical center. PATIENTS: Individuals undergoing SLB for suspected ILD. MEASUREMENTS AND RESULTS: We examined outcomes for subjects with a clinical diagnosis of ILD who had been designated to undergo SLB. Mortality (assessed at 30 and 90 days) following SLB represented the primary end point. Morbidity resulting from complications from SLB served as a secondary end point. The cohort included 83 patients (mean [+/- SD] age, 57.3 +/- 14.2 years; men, 57.8%). IPF was eventually diagnosed in slightly more than half of the subjects. Overall, 30-day and 90-day mortality rates were low (4.8% and 6.0%, respectively). Subjects with IPF did well with SLB (30-day mortality rate, 7.1%) and did not face a higher risk of either death or complications relative to individuals with non-IPF forms of ILD. The only predictors of perioperative mortality were either the need for mechanical ventilation (MV) at the time of SLB or being immunosuppressed prior to undergoing SLB. Excluding persons who met either criterion yielded an overall 90-day post-SLB mortality rate of 1.5% in persons with IPF. Approximately 40% of patients in whom IPF was eventually diagnosed were initially thought to have another form of ILD. CONCLUSIONS: Persons with IPF tolerate SLB well. Requiring MV or being immunosuppressed is associated with an increased risk for death following SLB. Safety concerns should not preclude referral for SLB in patients who are clinically suspected of having IPF.     

Chronic interstitial pneumonia in silicosis and mix-dust pneumoconiosis: its prevalence and comparison of CT findings with idiopathic pulmonary fibrosis

BACKGROUND: Increased prevalence of chronic interstitial pneumonia (CIP) is reported in dust-exposed subjects. We investigated the prevalence of CIP in silicosis and mixed-dust pneumoconiosis and sought morphologic differences of CIP between the pneumoconiosis and idiopathic pulmonary fibrosis (IPF). METHODS: We reviewed CT scans of 243 silicosis and mixed-dust pneumoconiosis patients to identify any cases of parenchymal lung lesions showing a CIP pattern, and compared the CT findings with those of 62 patients with IPF. Two observers independently scored CT images and classified the CT pattern as typical or not typical for IPF. Differences were sought between the groups using a nonparametric test, Fisher exact test, and a logistic regression analysis. A radiopathologic correlation was performed in 11 pneumoconiosis patients. RESULTS: Twenty-eight patients (11.5%) showed CIP on CT. Seven patients (25%) showed a pattern not typical of IPF, while the remaining patients showed a pattern typical of IPF, 11 of which were confirmed pathologically. The extent of fibrosis did not differ between the groups; however, patients with pneumoconiosis showed less traction bronchiectasis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.08 to 0.48; p < 0.001), more subpleural homogeneous attenuation (OR, 2.56; 95% CI, 1.55 to 4.23; p < 0.001), and fibrosis was more randomly distributed (OR, 315.38; 95% CI, 4.68 to 21244.63; p = 0.007). Pathologically, subpleural homogeneous attenuation corresponded to dense fibrosis often with abundant silicotic nodules. CONCLUSIONS: Prevalence of CIP in pneumoconiosis was approximately 12% on CT. One fourth of patients showed an atypical IPF pattern, and the others showed a typical IPF pattern.     

Overlap of interstitial pneumonia with autoimmune features with undifferentiated connective tissue disease and contribution of UIP to mortality

Background and objective

Criteria for interstitial pneumonia with autoimmune features (IPAF) were recently established for research purposes in a joint statement from the European Respiratory Society (ERS) and American Thoracic Society (ATS). We reviewed the utility of these criteria in patients previously diagnosed as broadly defined undifferentiated connective tissue disease (UCTD) and noted overlapping IPAF findings. Additional review was given to IPAF patients with usual interstitial pneumonia (UIP) on histopathology or radiology in terms of survival and outcome.

Methods

Patients with prior UCTD‐interstitial lung disease (ILD) were screened by ERS/ATS criteria for IPAF. Clinical data along with all‐cause mortality were collated and compared with selected idiopathic pulmonary fibrosis (IPF) patients from the same study period. Survival was compared between IPAF subgroups with and without UIP features.

Results

One hundred and one UCTD‐ILD subjects (91%) evaluated from 2005 to 2012 also met strict criteria for IPAF. Frequent clinical findings included Raynaud’s phenomenon, positive anti‐nuclear antibody (ANA) and non‐specific interstitial pneumonia (NSIP) pattern on chest computed tomography (CT). Nineteen had features of UIP either on histopathology or CT imaging. As compared with IPF, IPAF patients had overall better survival except in those with UIP features.

Conclusion

Current IPAF criteria encompassed the majority of broadly defined UCTD‐ILD and included those with UIP findings. Survival compared with IPF in those with UIP was similar. Further studies are necessary to refine IPAF definitions for clinical use and guide directed management strategies.

     

Pericardial abnormalities predict the presence of echocardiographically defined pulmonary arterial hypertension in systemic sclerosis-related interstitial lung disease

OBJECTIVES: To determine the prevalence and significance of pericardial abnormalities in systemic sclerosis (SSc)-related interstitial lung disease (ILD). METHODS: Retrospective study of 41 subjects with SSc-related ILD who underwent evaluation including thoracic high-resolution CT (HRCT) imaging, transthoracic echocardiography (TTE), and pulmonary function testing. HRCT review evaluated the pericardium for the presence of pericardial effusion (PEf), thickness of the anterior pericardial recess (APR) [abnormal defined as > 10 mm], and pericardial thickening as calculated by total pericardial score (TPS) [abnormal defined as > 8 mm]. Pulmonary arterial hypertension (PAH) was defined as a pulmonary artery pressure > 35 mm Hg estimated by TTE. RESULTS: Fifty-nine percent had an abnormal pericardium, 49% had a PEf, 56% had an abnormal APR, and 49% had an abnormal TPS. An abnormal pericardium was more common in men than women. Subjects with and without pericardial abnormalities were otherwise similar with respect to age, SSc classification, autoantibodies, ILD radiographic pattern, and presence of esophageal dilation. Both groups had similar median percentage of predicted total lung capacity, percentage of predicted FVC, percentage of predicted FEV(1), and percentage of predicted diffusion capacity of the lung for carbon monoxide. Subjects with pericardial abnormalities were more likely to have coexistent PAH (35% vs 75%; p = 0.02) and a higher median right ventricular systolic pressure (31 mm Hg vs 44 mm Hg; p = 0.03). Multiple logistic regression revealed that TPS was the best individual predictor of the presence of TTE-defined PAH. CONCLUSIONS: In patients with SSc-related ILD, pericardial abnormalities are commonly seen on HRCT, and their presence is strongly associated with echocardiographically defined PAH, with abnormal TPS as the best individual predictor.     

Ventilator settings and outcome of respiratory failure in chronic interstitial lung disease

BACKGROUND: While patients with interstitial lung disease (ILD) may be particularly susceptible to ventilator-induced lung injury, ventilator strategies have not been studied in this group of patients. PURPOSES: To describe the clinical course and outcome of patients with ILD and acute respiratory failure in relation to ventilatory parameters. METHODS: We retrospectively identified a cohort of ventilated patients with ILD who had been admitted to five ICUs at a single institution. We analyzed demographic data, pulmonary function test results, severity of illness, and the parameters of continuous ventilation for the initial 24 h after admission to the ICU. Primary outcomes were survival to hospital discharge and 1-year survival. Main results: Of 94 patients with ILD, 44 (47%) survived to hospital discharge and 39 (41%) were alive at 1 year. Nonsurvivors were less likely to be postoperative, had higher severity of illness, and were ventilated at higher airway pressures and lower tidal volumes. Step changes in positive end-expiratory pressure (PEEP) of > 10 cm H(2)O were attempted in 20 patients and resulted in an increase in plateau pressure (median difference, + 16 cm H(2)O; interquartile range [IQR], 9 to 24 cm H(2)O) and a decrease in respiratory system compliance (median difference, - 0.28 mL/kg/cm H(2)O; IQR, - 0.43 to - 0.13 mL/kg/cm H(2)O). The Cox proportional hazards model revealed that high PEEP (hazard ratio, 4.72; 95% confidence interval [CI], 2.06 to 11.15), acute physiology and chronic health evaluation (APACHE) III score predicted mortality (hazard ratio 1.33; 95% CI, 1.18 to 1.50), age (hazard ratio, 1.03; 95% CI, 1 to 1.05), and low Pao(2)/fraction of inspired oxygen ratio (hazard ratio, 0.96; 95% CI, 0.92 to 0.99) to be independent determinants of survival. CONCLUSION: Both severity of illness and high PEEP settings are associated with the decreased survival of patients with ILD who are receiving mechanical ventilation.     

Consolidation with a twisted appearance along the airways: A report of five cases of interstitial pneumonia

High-resolution CT showed areas of airspace consolidation with a twisted appearance of the airways, along with areas of peribronchial ground-glass attenuation and traction bronchiectasis, in five patients with interstitial pneumonia. These areas of airspace consolidation were termed “twisted consolidation” (TwC). The five patients included two patients receiving treatment for rheumatoid arthritis (RA), one patient with newly diagnosed RA, and one patient who subsequently showed RA. Three patients showed improvement after steroid administration. An association of TwC with RA is suspected, but further studies are necessary.     

Circulating thymus- and activation-regulated chemokine/CCL17 is a useful biomarker for discriminating acute eosinophilic pneumonia from other causes of acute lung injury

BACKGROUND: The presentation of acute eosinophilic pneumonia (AEP) closely resembles that of acute lung injury (ALI)/ARDS, including its idiopathic form, acute interstitial pneumonia (AIP). AEP usually lacks peripheral eosinophilia at the acute phase; therefore, the establishment of serum biomarkers for AEP would be clinically useful. METHODS: We measured the levels of thymus- and activation-regulated chemokine (TARC)/CCL17, eotaxin/CCL11, KL-6, and surfactant protein-D (SP-D) in serum for patients with acute parenchymal lung diseases including AEP (n = 17), AIP (n = 13), pneumonia-associated ALI/ARDS (n = 12), and alveolar hemorrhage (n = 7). To evaluate diagnostic ability, each marker was estimated by measuring the area under the receiver operating characteristic curve (AUC). RESULTS: Serum TARC/CCL17 levels of AEP patients were much higher than those of patients in other disease groups. More importantly, high circulating TARC/CCL17 levels were observed in AEP even at acute phase when peripheral eosinophilia was absent. TARC/CCL17 showed the largest AUC, and the TARC/CCL17 levels with cutoff points from 6,259 to 7,039 pg/mL discriminated AEP from other syndromes with sensitivity and specificity of 100%. The KL-6 level was low in most patients with AEP, and the sensitivity was 81.6% in cutoff with 100% specificity. The AUC for eotaxin/CCL11 and SP-D was small, with values of 0.73 (95% confidence interval [CI], 0.60 to 0.86) and 0.53 (95% CI, 0.31 to 0.64), respectively. CONCLUSIONS: This study indicates that the measurement of circulating TARC/CCL17 and KL-6 is useful for discriminating AEP from other causes of ALI.     

Follow-up study on pulmonary function and lung radiographic changes in rehabilitating severe acute respiratory syndrome patients after discharge

OBJECTIVES: To follow-up on the changes in lung function and lung radiographic pictures of severe acute respiratory syndrome (SARS) patients discharged from Xiaotangshan Hospital in Beijing (by regularly receiving examination), and to analyze retrospectively the treatment strategy in these patients. METHODS: Surviving SARS patients were seen at least twice within 3 months after discharge and underwent SARS-associated coronavirus (SARS-CoV) IgG antibody testing, pulmonary function testing, and chest radiography and/or high-resolution CT (HRCT) examinations at Chinese PLA General Hospital. The treatments received at Xiaotangshan Hospital were analyzed retrospectively and were correlated to later status. RESULTS: Positive SARS-Co virus IgG antibody results were seen in 208 of 258 patients, with 21.3% (55 of 258 patients) still having a pulmonary diffusion abnormality (D(LCO) < 80% of predicted). By comparing the 155 survivors with positive SARS-CoV IgG antibody results and D(LCO) > or = 80% predicted with the 50 patients with negative SARS-CoV IgG results, we found that 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality had endured a much longer course of fever and received larger doses of glucocorticoid, as well as higher ratios of oxygen inhalation and noninvasive ventilation treatment. For these patients, 51 of 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality underwent pulmonary function testing after approximately 1 month. D(LCO) improved in 80.4% of patients (41 of 51 patients). Of the patients with a lung diffusion abnormality, 40 of 51 patients showed lung fibrotic changes in the lung image examination and 22 patients (55%) showed improvement in lung fibrotic changes 1 month later. CONCLUSION: These findings suggest that lung fibrotic changes caused by SARS disease occurred mostly in severely sick patients and may be self-rehabilitated. D(LCO) scores might be more sensitive than HRCT when evaluating lung fibrotic changes.     

Airway nitric oxide in patients with cystic fibrosis is associated with pancreatic function, Pseudomonas infection, and polyunsaturated fatty acids

BACKGROUND: Airway nitric oxide (NO) is low or normal in cystic fibrosis (CF) patients. This may affect bacterial status since NO has antimicrobial properties. Arachidonic acid (AA), which is increased in the serum and airways of CF patients, has been shown to reduce NO levels. The aim of this study was to investigate whether airway NO level correlates with genotype and pancreatic function, and whether low airway NO level is associated with bacterial infection and increased serum AA level in CF patients. METHOD: Nasal NO (nNO) and exhaled NO (eNO) were measured according to the European Respiratory Society/American Thoracic Society standard in 59 CF patients aged 7 to 55 years, 80% of whom were pancreatic insufficient (PI) and 51% were chronically infected with Pseudomonas aeruginosa. RESULTS: PI CF patients had significantly lower nNO levels than pancreatic-sufficient (PS) patients. Airway NO level did not correlate with lung function or inflammatory parameters. PI patients chronically infected with P aeruginosa had significantly lower nNO levels than noninfected PI patients. nNO level correlated inversely with the AA/docosahexaenoic acid ratio, and eNO with the essential fatty acid (FA) deficiency index, which is the ratio between mead acid and AA. CONCLUSIONS: CF patients with PI, which is associated with more severe genotypes, had lower airway NO levels than patients with PS. Low NO level was correlated to chronic P aeruginosa infection, and an association was found between airway NO level and the abnormal serum phospholipid FA pattern.     

Respiratory bronchiolitis-interstitial lung disease: long-term outcome

BACKGROUND: The clinical and physiologic features of respiratory bronchiolitis (RB)-interstitial lung disease (ILD) have been previously described; however, the natural history and outcome have not been systematically evaluated. The majority of published reports consider RB-ILD to be a nonprogressive ILD that clinically improves with smoking cessation and antiinflammatory treatment. In this study, we sought to determine the outcome of RB-ILD patients with and without smoking cessation and with and without corticosteroid therapy. METHODS: Thirty-two RB-ILD cases confirmed by surgical lung biopsy were identified from a prospectively enrolled cohort of subjects with ILD. Initial and follow-up data on symptoms, physiology, treatment, and outcome were collected and analyzed. RESULTS: Kaplan-Meier analysis revealed that at least 75% of RB-ILD patients survived > 7 years after diagnosis. Clinical improvement occurred in only 28% of cases, and physiologic improvement occurred in 10.5% of cases. One patient died of progressive ILD, and two patients died of non-small cell lung cancer. While physiologic improvement was limited to those who had ceased smoking, corticosteroids and/or other immunosuppressive therapy had little effect on symptoms or physiology. CONCLUSIONS: This study shows that prolonged survival is common in RB-ILD. However, symptomatic and physiologic improvement occurs in only a minority of patients, and neither smoking cessation nor immunosuppressive therapy is regularly associated with clinically significant benefit.     

Zinc chloride (smoke bomb) inhalation lung injury: clinical presentations, high-resolution CT findings, and pulmonary function test results

STUDY OBJECTIVES: Zinc chloride smoke inhalation injury (ZCSII) is uncommon and has been rarely described in previous studies. We hypothesized that structural changes of the lung might correlate with pulmonary function. To answer this question, we correlated findings from high-resolution CT (HRCT) scan and the results of pulmonary function tests (PFTs) in patients with ZCSII. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENTS: Twenty patients who had been hospitalized with ZCSII-related conditions. MEASUREMENTS: The study included HRCT scan scores (0 to 100), static and dynamic lung volumes, and diffusing capacity of the lung for carbon monoxide (D(LCO)). RESULTS: HRCT scans and PFTs were performed initially after injury (range, 3 to 21 days) in all patients and during the follow-up period (range, 27 to 66 days) in 10 patients. The predominant CT scan findings were patchy or diffuse ground-glass opacities with or without consolidation. The majority of patients showed a significant reduction of FVC, FEV1, total lung capacity, and D(LCO), but normal FEV1/FVC ratio values. Changes of functional parameters correlated well with HRCT scan scores. Substantial improvements in CT scan abnormalities and pulmonary function were observed at follow-up. CONCLUSIONS: The majority of our patients with ZCSII presented with a predominant parenchymal injury of the lung that was consistent with a restrictive type of functional impairment and a reduction in Dlco rather than with obstructive disease. Our results suggest that HRCT scanning and pulmonary function testing may reliably predict the severity of ZCSII.     

Marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue: imaging findings in 21 patients

BACKGROUND: Few articles have been published on imaging findings of marginal zone B-cell lymphoma of bronchus-associated lymphoid tissue (BALT) of the lung. We present CT scan and 18F-fluorodeoxyglucose (FDG) PET scan findings of the disease. METHODS: From March 1995 to February 2007, 21 pretreatment patients (male patients, 9; female patients, 12; age range, 35 to 76 years; mean [+/- SD] age, 54 +/- 10.4 years) were seen who had pathologic diagnoses of marginal zone B-cell lymphoma of BALT. After CT scans were reviewed searching for specific patterns and distribution of parenchymal lung lesions, patients were classified as having the following four different patterns: (1) single nodular or consolidative; (2) multiple nodular or areas of consolidation; (3) bronchiectasis and bronchiolitis; and (4) diffuse interstitial lung disease (DILD) patterns. In six patients, in whom PET/CT scanning was performed, the pattern and the extent of maximum standardized uptake values (mSUVs) of FDG uptake were described. RESULTS: A single nodular or consolidative pattern was observed in 7 of 21 (33%) patients, multiple nodular or areas of consolidation were observed in 9 patients (43%), bronchiectasis and bronchiolitis were observed in 3 patients (14%), and DILD was observed in 2 patients (10%). On PET scans (n = 6), lesions showed heterogeneous FDG uptake in five patients and homogeneous uptake in one patient, with mSUVs ranging from 2.2 to 6.3 (mean mSUV, 4.2 +/- 1.48). CONCLUSIONS: Marginal zone B-cell lymphomas of BALT manifest diverse patterns of lung abnormality on CT scans, but single or multiple nodules or areas of consolidation are the main patterns that occur in a majority (76%) of patients. Most lesions show heterogeneous but identifiable FDG uptake on PET scans.     

Etiology of community-acquired pneumonia in hospitalized patients in chile: the increasing prevalence of respiratory viruses among classic pathogens

BACKGROUND AND STUDY OBJECTIVES: The range and relative impact of microbial pathogens, particularly viral pathogens, as a cause of community-acquired pneumonia (CAP) in hospitalized adults has not received much attention. The aim of this study was to determine the microbial etiology of CAP in adults and to identify the risk factors for various specific pathogens. METHODS: We prospectively studied 176 patients (mean [+/- SD] age, 65.8 +/- 18.5 years) who had hospitalized for CAP to identify the microbial etiology. For each patient, sputum and blood cultures were obtained as well as serology testing for Mycoplasma pneumoniae and Chlamydophila pneumoniae, urinary antigen testing for Legionella pneumophila and Streptococcus pneumoniae, and a nasopharyngeal swab for seven respiratory viruses. RESULTS: Microbial etiology was determined in 98 patients (55%). S pneumoniae (49 of 98 patients; 50%) and respiratory viruses (32%) were the most frequently isolated pathogen groups. Pneumococcal pneumonia was associated with tobacco smoking of > 10 pack-years (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2 to 5.4; p = 0.01). Respiratory viruses were isolated more often in fall or winter (28%; p = 0.011), and as an exclusive etiology tended to be isolated in patients >/= 65 years of age (20%; p = 0.07). Viral CAP was associated with antimicrobial therapy prior to hospital admission (OR, 4.5; 95% CI, 1.4 to 14.6). CONCLUSIONS: S pneumoniae remains the most frequent pathogen in adults with CAP and should be covered with empirical antimicrobial treatment. Viruses were the second most common etiologic agent and should be tested for, especially in fall or winter, both in young and elderly patients who are hospitalized with CAP.     

FEV1 performance among patients with acute asthma: results from a multicenter clinical trial

OBJECTIVE: To determine the ability of patients seen for acute asthma exacerbations in the emergency department (ED) to perform good-quality FEV(1) measurements. METHODS: Investigators from 20 EDs were trained to perform spirometry testing as part of a clinical trial that included standardized equipment with special software-directed prompts. Spirometry was done on ED arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient visits. MEASUREMENTS: Study performance criteria differed from American Thoracic Society (ATS) guidelines because of the population acuity and severity of illness as follows: ability to obtain acceptable FEV(1) measures (defined as two or more efforts with forced expiratory times >/= 2 s and time to peak flow < 120 ms or back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two highest acceptable FEV(1) values within 10% of each other). RESULTS: Of the 620 patients (age range, 12 to 65 years), > 90% met study acceptability criteria on ED arrival and 74% met study reproducibility criteria. Mean initial FEV(1) was 38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients met study acceptability and reproducibility criteria. Patients with severe airway obstruction (FEV(1) < 25% of predicted) were initially less likely to meet quality goals, but this improved with time. The site was also an independent predictor of quality. CONCLUSION: When staff are well trained and prompt feedback regarding adequacy of efforts is given, modified ATS performance goals for FEV(1) tests can be met from most acutely ill adolescent and adult asthmatics, even within the first hour of evaluation and treatment for an asthma exacerbation.     

Familial idiopathic pulmonary fibrosis: clinical features and outcome

STUDY OBJECTIVES: Familial idiopathic pulmonary fibrosis (FIPF) has been defined as idiopathic pulmonary fibrosis (IPF) occurring in two or more members of a family. The clinical course of FIPF has not been fully defined. Accordingly, the current study was undertaken to establish clinical, radiologic, and histologic features, and survival in a consecutive series of patients with FIPF. DESIGN: Retrospective analysis of clinical, radiologic, and pathologic data from a consecutive series of patients with FIPF who were seen at Mayo Medical Center. Survival in patients with FIPF was contrasted to that of previously characterized patients with nonfamilial IPF who were evaluated at our institution. SETTING: Tertiary referral medical center. PATIENTS: We screened 47 patients and family members with FIPF from 15 families who were identified between the years 1992 and 2002. We further analyzed the subgroup of FIPF patients that was composed of 27 patients from 15 families in whom the complete clinical course was monitored at our institution. MEASUREMENTS: All patients exhibited clinical features that were compatible with IPF and either compatible high-resolution CT (HRCT) scan findings or histologic evidence of usual interstitial pneumonia. Clinical data, including symptoms, physical findings, HRCT scan findings, lung function test results, biopsy results, and survival were abstracted from the clinical records. RESULTS: Compared to patients with nonfamilial IPF, patients with FIPF did not demonstrate any notable differences in clinical, radiologic, or pathologic features. We observed that the total number of affected members in a family with FIPF was a significant risk factor for earlier mortality (p = 0.0157; hazard ratio, 1.434). Overall, however, patients with FIPF had a statistically similar outcome to those patients with nonfamilial IPF. CONCLUSIONS: Although uncommon, FIPF represents a distinct syndrome, which has clinical features and patient survival rates that are similar to those of nonfamilial IPF.     

Antibiotics for bacteremic pneumonia: Improved outcomes with macrolides but not fluoroquinolones

BACKGROUND: The questions of whether the use of antibiotics that are active against atypical organisms is beneficial in the treatment of community-acquired pneumonia and of the potential mechanisms of any beneficial effects remain unresolved. Proposed mechanisms include activity against atypical organisms vs the immunomodulatory effects of these antibiotics. The study of outcomes of a large cohort of patients with bacteremic pneumonia provides a unique opportunity to address these questions by excluding patients with primary atypical infection. METHODS: We reviewed data from the charts of 2,209 Medicare patients who were admitted to hospitals across the United States from either home or a nursing facility with bacteremic pneumonia between 1998 and 2001. Patients were stratified according to the type of antibiotic treatment. Multivariate modeling was performed to assess the relationship between the class of antibiotic used and several outcome variables. RESULTS: The initial use of any antibiotic active against atypical organisms was independently associated with a decreased risk of 30-day mortality (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.59 to 0.98; p = 0.03) and hospital admission within 30 days of discharge (OR, 0.67; 95% CI, 0.51 to 0.89; p = 0.02). Further analysis revealed that the benefits of atypical treatment were associated with the use of macrolides, but not the use of fluoroquinolones or tetracyclines, with macrolides conferring lower risks of in-hospital mortality (OR, 0.59; 95% CI, 0.40 to 0.88; p = 0.01), 30-day mortality (OR, 0.61; 95% CI, 0.43 to 0.87; p = 0.007), and hospital readmission within 30 days of discharge (OR, 0.59; 95% CI, 0.42 to 0.85; p = 0.004). CONCLUSIONS: Initial antibiotic treatment including a macrolide agent is associated with improved outcomes in Medicare patients hospitalized with bacteremic pneumonia. These results have implications regarding the mechanism by which the use of a macrolide for treatment of pneumonia is associated with improved outcomes.     

Bronchoalveolar cellularity and interleukin-8 levels in measles bronchiolitis obliterans

BACKGROUND: Measles virus infection may progress to a chronic obstructive process including bronchiolitis obliterans (BO). This study investigates pulmonary cellular profiles and interleukin (IL)-8 levels in patients with BO following the measles. METHODS: BAL fluid was obtained from 12 children with BO who had a history of measles pneumonia during an outbreak in 2000 and 2001. BAL cell counts and differentials were compared to control patients as well as BAL IL-8 levels, which were measured by enzyme-linked immunosorbent assay. Immunohistochemical staining of BAL cells and three open-lung biopsy specimens were also analyzed for T-cell surface markers CD3, CD4, and CD8. RESULTS: BAL cellular profiles were characterized by a significantly increased percentage of neutrophils in the measles BO group (median, 16.0%) compared to the control group (2.3%) [p < 0.01]. BAL IL-8 levels were also markedly increased in the measles BO group (mean +/- SD, 418.6 +/- 286.0 pg/mL) compared to the control group (92.8 +/- 126.7 pg/mL) [p < 0.01]. BAL IL-8 levels correlated significantly with neutrophil percentages in both the measles BO group (r = 0.86, p = 0.000) and the control group (r = 0.79, p = 0.007). The lymphocyte subsets were characterized by a significantly increased number of CD8+ cells, resulting in a decreased CD4/CD8 ratio in the BAL and the biopsy specimens. CONCLUSION: These results suggest that pulmonary neutrophils and IL-8, along with CD8+ T lymphocytes may play an important role in the pathogenesis of BO after measles virus infection.     

The modified APACHE II score outperforms Curb65 pneumonia severity score as a predictor of 30-day mortality in patients with methicillin-resistant Staphylococcus aureus pneumonia

OBJECTIVE: To compare the predictive accuracy for 30-day mortality of the CURB65 score adopted by the British Thoracic Society and the simpler CRB65 score to APACHE (acute physiology and chronic health evaluation) II in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching hospital. PATIENTS: Adult patients requiring hospitalization identified to have MRSA pneumonia. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: Two hundred eighteen patients with MRSA pneumonia were identified over a 3-year period. Forty-four patients (20.2%) died during hospitalization. All three prediction rules had high negative predictive values but relatively low positive predictive values at most cut-off points examined. APACHE II had the greatest area under the receiver operating characteristic curve (0.805; 95% confidence interval [CI], 0.743 to 0.866) compared to CURB65 (0.634; 95% CI, 0.541 to 0.727) and CRB65 (0.643; 95% CI, 0.546 to 0.739) [p < 0.05 for both comparisons]. Similar results were obtained when the subgroups of community-acquired MRSA pneumonia and health-care-associated MRSA pneumonia were examined separately. CONCLUSIONS: APACHE II outperformed CURB65 and CRB65 for initial prognostic assessment in MRSA pneumonia.     

Lung function accurately predicts hypercapnia in patients with Duchenne muscular dystrophy

BACKGROUND: In patients with Duchenne muscular dystrophy (DMD), implementation of mechanical ventilation depends on sleep investigation and measurement of CO2 tension. The objective of this cross-sectional study was to determine which noninvasive lung function parameter best predicts nocturnal hypercapnia and diurnal hypercapnia in these patients. METHODS: According to transcutaneous CO2 (TcCO2) measurement, 114 DMD patients were classified into three groups: nocturnal hypercapnia (n = 38) [group N], diurnal hypercapnia (n = 39), despite nocturnal ventilation (group D), and 24-h normocapnia and spontaneous breathing (n = 37) [group S] as control. TcCO2 tension and lung function variables included vital capacity (VC) and maximal inspiratory pressure (MIP), and breathing pattern variables included tidal volume (Vt) and respiratory rate (RR), measured at the time of group inclusion. The rapid and shallow breathing index (RSBI [RR/Vt]) and Vt/VC ratio were calculated. Areas under the curve from the receiver operating characteristic (ROC) were calculated for those parameters. RESULTS: Compared to group S, lung function was significantly worse in group N and group D. VC, RR, and RSBI distinguished group S from group N by ROC comparison. Cut-off values of VC < or = 680 mL (ROC, 0.968), MIP < or = 22 cm H2O (ROC, 0.928), and Vt/VC > 0.33 (ROC, 0.923) accurately discriminated group D from group N, but RSBI, RR, and Vt did not. CONCLUSIONS: Lung function is useful to predict nocturnal hypercapnia in patients with DMD. Moreover, VC < 680 mL is very sensitive to predict daytime hypercapnia.