Variations in very preterm birth rates in 30 high-income countries: are valid international comparisons possible using routine data?

OBJECTIVE: Concerns about differences in registration practices across countries have limited the use of routine data for international very preterm birth (VPT) rate comparisons. DESIGN: Population-based study. SETTING: Twenty-seven European countries, the United States, Canada and Japan in 2010. POPULATION: A total of 9 376 252 singleton births. METHOD: We requested aggregated gestational age data on live births, stillbirths and terminations of pregnancy (TOP) before 32 weeks of gestation, and information on registration practices for these births. We compared VPT rates and assessed the impact of births at 22-23 weeks of gestation, and different criteria for inclusion of stillbirths and TOP on country rates and rankings. MAIN OUTCOME MEASURES: Singleton very preterm birth rate, defined as singleton stillbirths and live births before 32 completed weeks of gestation per 1000 total births, excluding TOP if identifiable in the data source. RESULTS: Rates varied from 5.7 to 15.7 per 1000 total births and 4.0 to 11.9 per 1000 live births. Country registration practices were related to percentage of births at 22-23 weeks of gestation (between 1% and 23% of very preterm births) and stillbirths (between 6% and 40% of very preterm births). After excluding births at 22-23 weeks, rate variations remained high and with a few exceptions, country rankings were unchanged. CONCLUSIONS: International comparisons of very preterm birth rates using routine data should exclude births at 22-23 weeks of gestation and terminations of pregnancy. The persistent large rate variations after these exclusions warrant continued surveillance of VPT rates at 24 weeks and over in high-income countries. TWEETABLE ABSTRACT: International comparisons of VPT rates should exclude births at 22-23 weeks of gestation and terminations of pregnancy.

Effectiveness of Rabbit Antithymocyte Globulin in Chronic Lung Allograft Dysfunction.

BACKGROUND: Rabbit antithymocyte globulin (rATG) therapy has been shown to be beneficial in lung transplant recipients as induction therapy for treating acute lung rejection; however, its role in chronic lung rejection has been reported only rarely. We evaluated the effectiveness of rATG therapy in slowing the progression of chronic lung allograft dysfunction (CLAD) syndrome. METHODS: We conducted a retrospective review of 25 lung transplant patients with CLAD who received rATG therapy in the Pulmonary Institute of Rabin Medical Center, Israel, between May 2005 and February 2016. Response to treatment was divided into 2 categories: stabilization, defined as a halting of the decline of forced expiratory volume in 1 second (FEV1) for ≥6 months after rATG therapy, and deterioration, defined as showing a continued decline in FEV1. RESULTS: Of 25 subjects, 8 (32%) were categorized as part of the stabilization group and 17 (68%) were categorized as showing continued deterioration. The stabilization group was older (61 ± 8 vs 44 ± 19 years) and showed longer survival rate after rATG therapy (930 ± 385 vs 414 ± 277 days). The stabilization group also demonstrated a lower mean white blood cell count (7.9 ± 1.8 vs 8.5 ± 2.9 × 10(9) cells/L) and lymphocyte count (0.37 ± 0.1 vs 0.55 ± 0.3 × 10(9) cells/L) during rATG treatment. The stabilization group also demonstrated a higher FEV1 after lung transplantation (91% ± 21% vs 75% ± 15.4%), at the beginning of rATG therapy (51% ± 11% vs 39% ± 9.6%) and at 6 months after rATG therapy follow-up (51% ± 9.1% vs 28% ± 7.6%). CONCLUSIONS: rATG was effective in stabilizing rejection progression in approximately one-third of our patients with CLAD. rATG therapy should be considered early in the course of CLAD. Randomized, controlled studies should be considered to confirm these findings.

Lobar distribution in non-cystic fibrosis bronchiectasis predicts bacteriologic pathogen treatment.

Non-cystic fibrosis bronchiectasis (NCFBr) is a major cause of morbidity due to frequent infectious exacerbations. We analyzed the influence of patient age and bronchiectasis location on the bacterial profile of patients with NCFBr. This retrospective cohort study included 339 subjects diagnosed with an infectious exacerbation of NCFBr during the 9-year period between January 2006 and December 2014. Bronchoalveolar lavage (BAL) cultures and high-resolution computed tomography scans (HRCT) were utilized to characterize the location of the bronchiectasis and bacteriologic pathogenic profile. In univariate logistic regression, the frequency of Haemophilus influenzae was higher in patients aged ≤64 years (OR = 0.969, p < 0.0001, 95 % CI 0.954-0.983), whereas the frequency of Pseudomonas aeruginosa (OR = 1.027, p = 0.008, 95 % CI 1.007-1.048) and Enterobacteriaceae (OR = 1.039, p = 0.01, 95 % CI 1.009-1.069) were significantly higher in patients aged >64 years. The lobar distribution of bronchiectasis in the subjects was 25.9 % in the right middle lobe (RML), 20.7 % in the right lower lobe (RLL), 20.4 % in the left lower lobe (LLL), 13.8 % in the lingula, 13 % in the right upper lobe (RUL), and 6.2 % in the left upper lobe (LUL). In the lower lobes, H. influenzae was the dominant species isolated, whereas in the RUL it was P. aeruginosa and in the LUL it was non- tuberculous mycobacterium (NTM). H. influenzae was more prevalent in younger patients, whereas P. aeruginosa, Enterobacteriaceae and NTM predominated in older patients. Different pathogens were associated with different lobar distributions. The RML, RLL and LLL showed a greater tendency to develop bronchiectasis than other lobes.

Outbreak of autoimmune disease in silicosis linked to artificial stone.

BACKGROUND: There is a well-established association between inhalational exposure to silica and autoimmune disease. We recently observed an outbreak of silica-related autoimmune disease among synthetic stone construction workers with silicosis referred for lung transplantation assessment. AIMS: To characterize the rheumatologic complications in silicosis within these highly exposed, clinically well-characterized patients. METHODS: We systematically reviewed data from all cases of silicosis due to synthetic stone dust referred to our pulmonary institute for lung transplant assessment, which represents the national centre for all such referrals. In addition to silicosis-specific data, we extracted data relevant to the clinical and serological manifestations of autoimmune diseases present in these patients. RESULTS: Of 40 patients in our advanced silicosis national data, we identified nine (23%) with findings consistent with various autoimmune diseases. Among these nine, three also had findings consistent with pulmonary alveolar proteinosis. Based on an expected autoimmune disease prevalence of 3% (based on the upper-end estimate for this group of diseases in European international data), the proportion of disease in our group represents a >7-fold excess (prevalence ratio 7.5; 99% confidence interval 2.6-16.7). CONCLUSIONS: These cases underscore the strong link between silicosis and multiple distinct syndromes of autoimmune diseases. Vigilance is warranted for the recognition of autoimmune complications in persons with known silicosis; so too is consideration of the occupational exposure history in persons presenting with manifestations of autoimmune disease.

Fear of childbirth in nulliparous and multiparous women: a population-based analysis of all singleton births in Finland in 1997-2010.

OBJECTIVE: To identify risk factors for fear of childbirth (FOC) according to parity and socioeconomic status, and to evaluate associations between FOC and adverse perinatal outcomes. DESIGN: A cohort study. SETTING: The Finnish Medical Birth Register. POPULATION: All 788 317 singleton births during 1997-2010 in Finland. METHODS: Fear of childbirth was defined according to the International Classification of Diseases code O99.80, and its associations with several risk factors and perinatal outcomes were analysed by multivariable logistic regression. MAIN OUTCOME MEASURES: Prevalence of, risk factors for and outcomes of FOC. RESULTS: Fear of childbirth was experienced by 2.5% of nulliparous women and 4.5% of multiparous women. The strongest risk factors for FOC in nulliparous women were depression [adjusted odds ratio (aOR), 6.35; 95% confidence interval (CI), 5.25-7.68], advanced maternal age (aOR, 3.78; 95% CI, 3.23-4.42) and high or unspecified socioeconomic status. In multiparous women, the strongest risk factors for FOC were depression (aOR, 5.47; 95% CI, 4.67-6.41), previous caesarean section (CS) (aOR, 3.02; 95% CI, 2.93-3.11) and high or unspecified socioeconomic status. Among both nulliparous and multiparous women, FOC was associated with higher rates of CS (3.3-fold and 4.5-fold higher, respectively) and a lower incidence of low birthweight (<2500 g), small for gestational age babies, preterm birth and low Apgar scores at 1 minute. CONCLUSIONS: High and unspecified socioeconomic status, advanced maternal age and depression are predisposing factors for FOC regardless of parity. Among multiparous women, a previous CS increases vulnerability to FOC. FOC is associated with increased rates of CS, but does not adversely affect other pregnancy outcomes.

Bronchial anthracofibrosis: treatment using airway stents.

Bronchial anthracofibrosis is a rare disease characterised by chronic bronchial inflammation, with bronchoscopic findings showing dark anthracotic pigmentation on the bronchial mucosa in conjunction with bronchial narrowing or obliteration which causes stenosis of the airways. We describe our experience in two patients with severe bronchial anthracofibrosis and discuss a novel treatment of the stenotic bronchi using endobronchial stents.

Does side matter? Effect of single lung transplant laterality on outcomes.

BACKGROUND: Previous works have suggested that recipients of left single lung transplant (SLT) have a worse outcome than those receiving right SLT. We evaluated the effect of SLT laterality on outcomes. METHODS: We performed a retrospective study of SLT recipients followed up at our center. One hundred and nineteen patients were reviewed (53 left SLT, 66 right SLT). We extracted data on lung function, exercise capacity, relative graft perfusion, airway complications, acute rejection episodes, infections and mortality. RESULTS: There was no significant difference between right and left lung recipients with regard to baseline demographic and physiological characteristics. Lung function, exercise capacity and relative graft perfusion improved in both groups following transplantation. We observed a higher graft perfusion in right-sided grafts compared to left ( P = 0.048). There was no significant difference between the two groups in physiological outcomes, rejection or infection episodes, the presence of chronic rejection or mortality. We observed a statistically higher need for bronchial stent insertion during early follow-up amongst the left lung recipients ( P = 0.022). CONCLUSIONS: Both right and left lungs are equally suitable for transplantation. The left-sided bronchial anastomosis may be more vulnerable to complications.

Comparison of isoniazid monoresistant tuberculosis with drug-susceptible tuberculosis and multidrug-resistant tuberculosis.

Limited data exist about the clinical characteristics of Mycobacterium tuberculosis (TB) isolates with resistance to isoniazid (IZN). We describe the demographic and clinical characteristics and risk factor information for persons with IZN monoresistant (resistant to isoniazid) TB compared with drug-susceptible TB and multidrug-resistant (MDR) TB. From 2002 to 2009, 590 cases of TB were diagnosed. Of these, 44 (7.5%) developed MDR-TB and 38 (6.4%) had IZN monoresistant TB. Among the IZN monoresistant TB patients, more common demographic characteristics were former resident of the Soviet Union immigrant, smoker, and previous history of TB (p = 0.005, 0.025, and 0.005, respectively), while HIV, weight loss, and hemoptysis were less common (p = 0.005 for all parameters). The mean length of treatment was 24 ± 4 months for MDR-TB, 10 ± 3 months for IZN monoresistant TB cases, and 8 ± 2 months for all other TB cases. The directly observed therapy (DOT) rate was similar in all three groups. However, treatment failure, completion of TB treatment, and mortality were all similar in drug-susceptible TB and higher in MDR-TB. In multivariate analysis, only a history of previous TB (odds ratio [OR] 1.4; 95% confidence interval [CI]: 1.2-1.6) was significantly associated with IZN monoresistant TB. IZN monoresistant TB has distinct characteristics. However, the length of treatment and outcome are similar to drug-susceptible TB cases.

Biologic lung volume reduction therapy for advanced homogeneous emphysema.

This report summarises phase 2 trial results of biologic lung volume reduction (BioLVR) for treatment of advanced homogeneous emphysema. BioLVR therapy was administered bronchoscopically to 25 patients with homogeneous emphysema in an open-labelled study. Eight patients received low dose (LD) treatment with 10 mL per site at eight subsegments; 17 received high dose (HD) treatment with 20 mL per site at eight subsegments. Safety was assessed in terms of medical complications during 6-month follow-up. Efficacy was assessed in terms of change from baseline in gas trapping, spirometry, diffusing capacity, exercise capacity, dyspnoea and health-related quality of life. There were no deaths or serious medical complications during the study. A statistically significant reduction in gas trapping was observed at 3-month follow-up among HD patients, but not LD patients. At 6 months, changes from baseline in forced expiratory volume in 1 s (-8.0+/-13.93% versus +13.8+/-20.26%), forced vital capacity (-3.9+/-9.41% versus +9.0+/-13.01%), residual volume/total lung capacity ratio (-1.4+/-13.82% versus -5.4+/-12.14%), dyspnoea scores (-0.4+/-1.27 versus -0.8+/-0.73 units) and St George's Respiratory Questionnaire total domain scores (-4.9+/-8.3 U versus -12.2+/-12.38 units) were better with HD than with LD therapy. BioLVR therapy with 20 mL per site at eight subsegmental sites may be a safe and effective therapy in patients with advanced homogeneous emphysema.

Decline in pulmonary function in patients with breast cancer receiving dose-dense chemotherapy: a prospective study.

BACKGROUND: Prompted by complaints of dyspnea in breast cancer patients receiving adjuvant dose-dense chemotherapy (DDC), we sought to evaluate the possible association of DDC with pulmonary dysfunction. PATIENTS AND METHODS: A total of 34 consecutive patients receiving adjuvant DDC were enrolled. The chemotherapy regimen consisted of i.v. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) (AC) every 14 days x4 with growth factor support followed by weekly i.v. paclitaxel 80 mg/m(2) x12. The following parameters were prospectively measured before and after the AC protocol (P1, P2) and at completion of paclitaxel treatment (P3): presence of dyspnea, blood pressure, pulse rate, hemoglobin, erythrocyte sedimentation rate, C-reactive protein level, cardiac ejection fraction, and pulmonary function. Repeated measures analysis was used to evaluate differences among the time points, and paired t-test was used to evaluate differences between consecutive time points. RESULTS: Although only five patients (15%) complained of dyspnea, there was a significant decrease in mean carbon monoxide diffusing capacity (DLCO), in all patients from P1 (22.09 ml/min/mmHg) to P3 (15 ml/min/mmHg) and in 29 of 32 patients (90.6%) from P1 to P2 (15.96 ml/min/mmHg) (P<0.001). CONCLUSIONS: DDC is associated with a statistical significant reduction in DLCO. Awareness of this potential toxicity may be important in women with preexisting lung disease.

Pulmonary Mycobacterium simiae infection: comparison with pulmonary tuberculosis.

To identify the clinical and radiological features distinguishing Mycobacterium simiae respiratory infection from pulmonary tuberculosis, the demographics, underlying conditions, and clinical and radiological findings of 121 consecutive patients with pulmonary tuberculosis and 102 with M. simiae respiratory infection were compared retrospectively. In the M. simiae group, the patients were older (mean age 69 +/- 16 years vs. 47 +/- 21 years, p = 0.0001), with a female predominance (62% vs. 45%, p = 0.008). Only 4% were of Ethiopian origin compared to 25% of the tuberculosis group (p = 0.0001). M. simiae infection was associated with significantly higher rates of smoking history, underlying chronic obstructive pulmonary disease, zero human immunodeficiency virus (HIV) infection compared to 10% in the tuberculosis group (p = 0.001), blunted symptoms, and noncavitary infiltrates in the lower/middle lobes on chest X-ray. HIV-negative patients with M. simiae respiratory infection are distinguishable from patients with pulmonary tuberculosis by several demographic, clinical, and radiological features. These findings have important diagnostic and therapeutic implications.

Absence of human herpesvirus 8 DNA sequences in lung biopsies from Israeli patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary hypertension is a severe pulmonary vascular disease leading to rapid deterioration and death. Histological and clinical evidence suggests that smooth muscle proliferation is part of the pathogenesis of the disease. Human herpesvirus 8 (HHV-8) is a gamma-herpesvirus that is implicated in malignancies and in Kaposi's sarcoma. Recently, the association of HHV-8 with idiopathic pulmonary arterial hypertension (PAH) has been found. OBJECTIVE: The aim of this study was to investigate the presence of HHV-8 in the lung tissue of Israeli patients with PAH. METHOD: The presence of HHV-8 sequences was investigated by polymerase chain reaction examination in 6 biopsies of patients with pulmonary hypertension. Three patients had idiopathic pulmonary hypertension, 2 patients pulmonary venoocclusive disease, and 1 patient pulmonary hypertension associated with mixed connective tissue disease. RESULT: We did not find any association between HHV-8 and PAH in these Israeli patients, as all the samples were negative for polymerase chain reaction. CONCLUSION: Our findings, together with the epidemiological data of HHV-8 prevalence and incidence rates of Kaposi's sarcoma and PAH in Israel, provide further evidence which argues against an association between HHV-8 infection and PAH.

Differentiation of Mycobacterium kansasii infection from Mycobacterium tuberculosis infection: comparison of clinical features, radiological appearance, and outcome.

This retrospective study sought to systematically identify clinical and radiological features differentiating Mycobacterium kansasii from Mycobacterium tuberculosis infection. The sample included matched patients with a culture-positive diagnosis of M. tuberculosis infection (n = 121) or M. kansasii infection (n = 62) derived from the databases of two tuberculosis centers. Data on patient background and clinical features were collected, and chest radiographs were analyzed. Sixty percent of the M. kansasii group were native Israelis compared to 15% of the M. tuberculosis group (p = 0.0001). M. tuberculosis infection was associated with a higher rate of human immunodeficiency virus (HIV) infection (p = 0.03) and M. kansasii infection with a higher rate of lung disease (p = 0.0001). M. tuberculosis infection was characterized by a higher likelihood of bilateral disease (p = 0.005), pleural effusions, and lymphadenopathy (p = 0.006 and p = 0.001, respectively). There were ten deaths, all in the M. tuberculosis group. On multivariate logistic regression, the presence of chronic obstructive pulmonary disease and associated lung disease were significant predictors of M. kansasii infection. The findings show that there are group differences between the clinical features of the two infections. In the setting of pulmonary mycobacterial infection, the presence of coinfection with HIV, bilateral disease, pleural effusion, and lymphadenopathy make M. kansasii infection very unlikely.

Quantitative lung perfusion following single lung transplantation.

BACKGROUND: Following successful lung transplantation, most of the lung perfusion, as well as ventilation, is shifted towards the transplanted lung. We investigated the changes in perfusion during exercise in lung transplant recipients. PATIENTS AND METHODS: Twelve patients were included in the study. Six patients had emphysema and 6 patients had idiopathic pulmonary fibrosis (IPF). Patients underwent two upright lung perfusion scans: the first at rest and the second during a maximal cardiopulmonary exercise test. Lung perfusion was assessed in each lung and regionally. RESULTS: At rest, patients with emphysema had 83.3 +/- 8 % of total perfusion to the transplanted side and 16.7 +/- 8 % to the native lung, while in the IPF patients, it was 68.7 +/- 12 and 32.7 +/- 10 %, respectively ( P = 0.028). At peak exercise, perfusion shifted from the transplanted lung to the native lung ( P = 0.0095) both in emphysema and IPF patients. CONCLUSIONS: Following successful lung transplantation, most of the perfusion is directed towards the transplanted lung. During exercise, there was a small but significant shift towards the native lung. These findings highlighted the important role of the native lung during maximal exercise.

Use of noninvasive tools in primary pulmonary hypertension to assess the correlation of right ventricular function with functional capacity and to predict outcome.

UNLABELLED: Most patients with Primary Pulmonary Hypertension (PPH) have severe exertional limitation which ultimately leads to right heart failure and death. The purpose of the study was to assess the correlation between right ventricular (RV) systolic and diastolic noninvasive variables and exercise tolerance, as well as the predictors of adverse outcome in treated patients. METHODS: We prospectively studied 29 patients, 17 with PPH and 12 with PPH due to collagen disease. RV parameters were assessed by echocardiography and Radionuclide ventriculography. Pulmonary function and clinical profile were assessed by 6 min walk test and NYHA class. The patients were followed-up during 2 years for cardiac death and cardiac deterioration. RESULTS: Mean age was 51 +/- 15 years, 22 (78%) women. NYHA class1 in 2 pts, class 2 in 17, class 3 in 8 and class 4 in 2 pts. Pulmonary function (DLCO) was low in 25 (86%) pts, mean 22 +/- 48%. Six minutes walk distance was 358 +/- 132 m, RVEF was 34 +/- 11% (range 16-51%). Among RV variables, RVEF, RA area and TR were independently correlated to 6 min walk. Within follow up of 2 years, there were 10 patients with adverse outcome (4 deaths and 6 deteriorated to NYHA class 3 and 4). Among all clinical and noninvasive variables, RVEF only was correlated to adverse outcome. CONCLUSION: The noninvasive tests of RVEF, RA size and TR were closely correlated to exercise tolerance. However, among the various clinical, functional and RV variables, RVEF was the only variable correlated with adverse outcome in pts with PPH.

Redefining idiopathic interstitial lung disease into occupational lung diseases by analysis of chemical composition of inhaled dust particles in induced sputum and/or lung biopsy specimens.

There has been increased public awareness of the potential danger from exposure to hazardous dust in various occupations. This study aims to validate the qualitative analysis of scanning electron microscopy (SEM) of lung samples by 1) correlation of induced sputum (IS) findings to clinical findings, 2) comparing hazardous particles in IS to those in biopsied lung specimens, and 3) assessing whether the particles present in the lungs of transplanted patients correlate with occupational history of dust exposure. Forty patients with occupational history were included; of whom 35 filled in questionnaires. Twenty-four of them had SEM analysis of their IS, and 11 of these 24 also had SEM analysis of their lung tissue. Another 11 lung biopsies from patients with occupational history were scanned by SEM and compared with 10 lung biopsies from patients with no occupational history. SEM analysis of IS was as efficient for detecting hazardous particles as was SEM analysis of lung tissue; silica was detected better in sputum. Exposure to silica was the main chemical element associated with a high likelihood to show abnormalities in IS (Odds ratio 19.41 CI = 0.270-1398.33). The average number of detected hazardous chemical elements in patients with an occupational history of exposure was 4 +/- 1.61 in IS and 3.55 +/- 2.02 in lung tissue (P = 0.57); it was 1.5 +/- 0.85 from transplanted occupationally exposed patients compared with 0.36 +/- 0.67 in transplanted non-exposed patients (P = 0.003). SEM analysis of particles in IS and lung tissue can elucidate the causative agent(s) of otherwise idiopathic interstitial lung disease among occupationally exposed workers.

Normal D-dimer levels in patients with latent tuberculosis infection.

Studies have demonstrated a link between acute pulmonary tuberculosis and a hypercoagulable state, but there are no data on the coagulation state of patients with latent tuberculosis infection (LTI). The present prospective observational study was designed to help fill this gap. The sample included 84 patients (high school students and adults) with suspected LTI referred for the purified protein derivative (PPD) test. Results were read according to the criteria of the American Thoracic Society. Blood samples were collected at admission and assayed for D-dimer, the marker of the coagulation state, with the quantitative Miniquant test. D-dimer values were correlated with the PPD status and clinical parameters. Fifty-seven patients tested positive for LTI and 27 tested negative. There was no significant difference in D-dimer level between these groups (341 +/- 106 and 360 +/- 60 microg/ml, respectively). No significant correlation was found between D-dimer level and PPD status, patient age or occupation (health care worker or not), or clinical indication for the tuberculin test. The normal D-dimer levels in this series suggest that low-level inflammations such as LTI do not lead to a hypercoagulable state.