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Lower FEV(1) in non-COPD, nonasthmatic subjects: association with smoking, annual decline in FEV(1), total IgE levels, and TSLP genotypes.

Few studies have investigated the significance of decreased FEV(1) in non-COPD, nonasthmatic healthy subjects.

We hypothesized that a lower FEV(1) in these subjects is a potential marker of an increased susceptibility to obstructive lung disease such as asthma and COPD. This was a cross-sectional analysis of 1505 Japanese adults.

We divided the population of healthy adults with no respiratory diseases whose FEV(1)/FVC ratio was ≥70% (n = 1369) into 2 groups according to their prebronchodilator FEV(1) (% predicted) measurements: <80% (n = 217) and ≥80% (n = 1152). We compared clinical data - including gender, age, smoking habits, total IgE levels, and annual decline of FEV(1) - between these 2 groups. I

n addition, as our group recently found that TSLP variants are associated with asthma and reduced lung function, we assessed whether TSLP single nucleotide polymorphisms (SNPs) were associated with baseline lung function in non-COPD, nonasthmatic healthy subjects (n = 1368). Although about half of the subjects with lower FEV(1) had never smoked, smoking was the main risk factor for the decreased FEV(1) in non-COPD, nonasthmatic subjects. However, the subjects with lower FEV(1) had a significantly higher annual decline in FEV(1) independent of smoking status.

Airflow obstruction was associated with increased levels of total serum IgE (P = 0.029) and with 2 functional TSLP SNPs (corrected P = 0.027-0.058 for FEV(1)% predicted, corrected P = 0.015-0.033 for FEV(1)/FVC). This study highlights the importance of early recognition of a decreased FEV(1) in healthy subjects without evident pulmonary diseases because it predicts a rapid decline in FEV(1) irrespective of smoking status.

Our series of studies identified TSLP variants as a potential susceptibility locus to asthma and to lower lung function in non-COPD, nonasthmatic healthy subjects, which may support the contention that genetic determinants of lung function influence susceptibility to asthma.

Detection of microorganisms in exhaled breath condensate during acute exacerbations of COPD.

Exhaled breath condensate (EBC) is a noninvasive method to assess airway biology. The aim of the present study was to evaluate EBC for the detection of microbial nucleic acids during acute exacerbations of COPD (AECOPD). Bacterial nucleic acids can be identified in EBCs of COPD patients with exacerbations, however, the results differed significantly from those of sputum.

Background and objective:  One hallmark of chronic obstructive pulmonary disease (COPD) is colonization and infection of the lung. Acute exacerbations of COPD (AECOPD) are acute deteriorations of the chronic disease and are associated with a change of the pulmonary microbial balance. The collection of exhaled breath condensate (EBC) can be used to noninvasively determine markers of lung disease. The aim of the present study was to compare the results of assays based on the detection of microbial nucleic acids from exhaled breath condensate (EBC) and from spontaneous sputum in patients with AECOPD.

Methods:  EBCs and sputa of 29 adults with AECOPD were obtained. Isolated DNA or RNA were used as starting material for the PCR assays to detect Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, Legionella pneumophila,Mycoplasma pneumoniae,Chlamydia pneumoniae, influenza viruses (AH 1, AH 3) and respiratory syncytial virus.

Results:  Bacterial or viral nucleic acids were identified in 14 EBCs and 21 sputa from 29 patients. Results from EBC did not correlate well with those from sputum. Viral and S. pneumoniae nucleic acids were detected only in sputum, whereas L. pneumophila DNA was only found in EBC. In 3 EBCs and 10 sputa nucleic acids of more than one microorganism was detected.

Conclusions:  Bacterial nucleic acids can be identified in EBCs of COPD patients with exacerbations. The results obtained from EBC and sputum did not correlate well.

Lung Transplantation.

First performed in 1963, lung transplantation is approaching the half-century mark. With over 32,000 procedures having been carried out worldwide, lung transplantation has become the standard of care for select patients with advanced lung diseases of various non-malignant etiologies. Indications for transplantation have broadened over the years and selection criteria have become less restrictive.

A relatively scarce donor pool limits wider application of this therapy but this is being addressed in part through relaxation of donor selection criteria, donor management protocols that preserve and optimize lung function, and development of ex vivo perfusion techniques to "recondition" suboptimal organs. Bilateral lung transplantation has become the procedure of choice for most indications, though its preferential use in patients with idiopathic pulmonary fibrosis remains controversial.

Post-transplantation survival has steadily improved, but significant constraints on long-term survival persist as evidenced by a median survival rate that currently stands at 5.7 years. This has brought into focus the question of whether and for whom transplantation actually confers a survival advantage, a question that in the absence of randomized trials can only be answered with statistical modeling. Primary graft dysfunction, infection, and bronchiolitis obliterans syndrome are common complications encountered by the lung transplant recipient and major impediments to long-term survival.

This review provides an overview of the current status of lung transplantation, highlighting both the many advances that have taken place as well as the challenges that remain.

New pharmacological treatments for patients with chronic obstructive pumonary disease (copd).

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized mainly by pulmonary airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with abnormal inflammatory response of the lung to noxious particles or gasses. New different pharmacological approaches to decrease inflammation of the airways and consequently disease progression and increase airway obstruction reversibility have been developed.

Methods and Results. A literature search using PubMed, Science Direct, EBSCO and free patents on line for the years 2000-2010.

Conclusions. Recent discoveries in the physiology and pathology of airways diseases have served to generate potential new drugs for the treatment of COPD patients. Several substances that block or activate specific pathways and receptors the aim of which is to decrease inflammation and increase airway obstruction reversibility are being used in different clinical protocols and hopefully will be available for patients in the near future.

Pediatric asthma controller therapy.

The treatment of children with asthma has historically relied upon expert opinion using data extrapolated from adult studies. Over the past few years, landmark studies have been completed providing healthcare professionals with evidence on which a reasonable approach can be made for children suffering from this common and serious disease. Asthmatic phenotype in children, unlike adults, tends to differ according to age, which must be taken into account as well as triggers, severity, and level of control. The care of the child with asthma is complex, but accumulating data have demonstrated that we are on the right path for optimizing control while reducing the burden of side effects.

The newest Global Initiative for Asthma (GINA) guidelines, as well as recent updates from the landmark CAMP (Childhood Asthma Management Program) study and information from the PACT (Pediatric Asthma Control Trial) and budesonide/formoterol controller and reliever studies, along with recent comparisons of higher dose inhaled corticosteroids (ICS), and ICS/long-acting β(2)-adrenoceptor agonist (LABA) combination and leukotriene receptor antagonist (LTRA) therapies in children have clarified a few of the big questions in pediatric asthma. For children with asthma aged 5 years and older, the CAMP trial demonstrated that regular use of ICS reduces the frequency of symptoms; however, height was adversely affected and there is no evidence for altering the natural history of asthma.

In patients aged 6 years and over whose asthma is uncontrolled on ICS alone, combination therapy with ICS and a LABA has been recently compared with the use of higher dose ICS and the addition of an LTRA in pediatric patients. The addition of a LABA statistically will be of most benefit; however, some children will have optimal control with doubling the baseline dose of ICS or addition of an LTRA. Use of budesonide/formoterol as a controller and reliever therapy extends the time to first exacerbation versus contemporary use of this medication in patients aged 4 years and older.

Ciclesonide, a newer ICS, has demonstrated acceptable efficacy but has the added benefit of not affecting growth. Certainly, with mounting evidence, the care-map in pediatric asthma control is becoming clearer.

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