Comparison of particles in exhaled air and multiple breath washout for assessment of small airway function in children with cystic fibrosis.

Background: The introduction of modulator therapy for cystic fibrosis (CF) has led to an increased interest in the detection of small airway disease (SAD) as sensitive marker of treatment response. The particles in exhaled air (PExA) method, which records exhaled particle mass (PEx ng/L) and number (PExNR), detects SAD in adult patients. Our primary aim was to investigate if PExA outcomes in children with CF are different when compared to controls and associated with more severe disease.

Non-tuberculous mycobacteria disease pre-lung transplantation: A systematic review of the treatment regimens and duration pre- and post-transplant.

Background: There is lack of consensus on non-tuberculous mycobacteria pulmonary disease (NTM-PD) treatment regimen and duration in patient listed for lung transplantation (LTx). We conducted a systematic review on treatment regimen and duration pre- and directly post-LTx, for patients with known NTM-PD pre-LTx. Additionally, we searched for risk factors for NTM disease development post-LTx and for mortality.

Pulmonary arterial hypertension associated with pulmonary arteriovenous malformations and pulmonary veno-occlusive disease: A devastating combination.

We describe a case of an adolescent male with the rare combination of pulmonary arterial hypertension (PAH) and pulmonary arteriovenous malformations (PAVM's) without confirmed hereditary hemorrhagic telangiectasia (HHT). The patient showed clinical deterioration on standard vasodilator therapy, leading us to question our initial diagnosis. Post-mortem evaluation confirmed the presence of pulmonary veno-occlusive disease of which no conclusive signs were recognized at diagnostic work-up.

Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation.

Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates.

Paraneoplastic pemphigus associated with post-transplant lymphoproliferative disorder after small bowel transplantation.

Background: PNP is a malignancy-associated autoimmune mucocutaneous syndrome due to autoantibodies against plakins, desmogleins, and other components of the epidermis and basement membrane of epithelial tissues. PNP-causing malignancies comprise mainly lymphoproliferative and hematologic neoplasms. PNP is extremely rare, especially in children.

New insights in phenotype and treatment of lung disease immuno-deficiency and chromosome breakage syndrome (LICS).

We report five patients with lung disease immuno-deficiency and chromosome breakage syndrome (LICS) but without recurrent infections and severe immunodeficiency. One patient had extended survival to 6.5 years.

Differences in lung clearance index and functional residual capacity between two commercial multiple-breath nitrogen washout devices in healthy children and adults.

Multiple-breath nitrogen washout (MBNW) and its clinical parameter lung clearance index (LCI) are gaining increasing attention for the assessment of small airway function. Measurement of LCI relies on accurate assessment of functional residual capacity (FRC). The EasyOne Pro LAB (ndd) and Exhalyzer D (EM) are two commercially available MBNW devices.

Fontan Circulation over Time.

The unique, unphysiological Fontan circulation is associated with an impaired functional status of the patients that is suggested to deteriorate over time. Unfortunately, previous studies did not integrate both pulmonary and cardiac determinants of functional status. In addition, a comparison with the natural decrease in exercise capacity in healthy subjects (in both children and adults) is lacking.

Protocadherin-1 Localization and Cell-Adhesion Function in Airway Epithelial Cells in Asthma.

Background: The asthma gene PCDH1 encodes Protocadherin-1, a putative adhesion molecule of unknown function expressed in the airway epithelium. Here, we characterize the localization, differential expression, homotypic adhesion specificity and function of PCDH1 in airway epithelial cells in asthma.

Methods: We performed confocal fluorescence microscopy to determine subcellular localization of PCDH1 in 16HBE cells and primary bronchial epithelial cells (PBECs) grown at air-liquid interface.

Protocadherin-1 binds to SMAD3 and suppresses TGF-β1-induced gene transcription.

Genetic studies have identified Protocadherin-1 (PCDH1) and Mothers against decapentaplegic homolog-3 (SMAD3) as susceptibility genes for asthma. PCDH1 is expressed in bronchial epithelial cells and has been found to interact with SMAD3 in yeast two-hybrid (Y2H) overexpression assays. Here, we test whether PCDH1 and SMAD3 interact at endogenous protein levels in bronchial epithelial cells and evaluate the consequences thereof for transforming growth factor-β1 (TGF-β1)-induced gene transcription.

Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.

Protocadherin-1 (PCDH1) is a novel susceptibility gene for airway hyperresponsiveness, first identified in families exposed to cigarette smoke and is expressed in bronchial epithelial cells. Here, we asked how mouse Pcdh1 expression is regulated in lung structural cells in vivo under physiological conditions, and in both short-term cigarette smoke exposure models characterized by airway inflammation and hyperresponsiveness and chronic cigarette smoke exposure models. Pcdh1 gene-structure was investigated by Rapid Amplification of cDNA Ends.

Untargeted lipidomic analysis in chronic obstructive pulmonary disease. Uncovering sphingolipids.

Rationale: Cigarette smoke is the major risk factor in the development of chronic obstructive pulmonary disease (COPD). Lipidomics is a novel and emerging research field that may provide new insights in the origins of chronic inflammatory diseases, such as COPD.

Objectives: To investigate whether expression of the sputum lipidome is affected by COPD or cigarette smoking.

Diminished expression of multidrug resistance-associated protein 1 (MRP1) in bronchial epithelium of COPD patients.

Cigarette smoke is the principal risk factor for chronic obstructive pulmonary disease (COPD). Multidrug resistance proteins, such as multidrug resistance-associated protein-1 (MRP1), P-glycoprotein (P-gp), and lung resistance-related protein (LRP), may protect against oxidative stress and toxic compounds generated by cigarette smoking. Expression of MRP1, P-gp, and LRP was evaluated in bronchial epithelium of two study groups of COPD patients and their controls and was associated with disease status and smoking history.

Association of current smoking with airway inflammation in chronic obstructive pulmonary disease and asymptomatic smokers.

Background: Inflammation in the airways and lung parenchyma underlies fixed airway obstruction in chronic obstructive pulmonary disease. The exact role of smoking as promoting factor of inflammation in chronic obstructive pulmonary disease is not clear, partly because studies often do not distinguish between current and ex-smokers.

Methods: We investigated airway inflammation in sputum and bronchial biopsies of 34 smokers with chronic obstructive pulmonary disease (9 Global initiative for Chronic Obstructive Lung Disease stage 0, 9 stage I, 10 stage II and 6 stage III) and 26 asymptomatic smokers, and its relationship with past and present smoking habits and airway obstruction.

Acute effects of cigarette smoking on inflammation in healthy intermittent smokers.

Background: Chronic smoking is the main risk factor for chronic obstructive pulmonary disease. Knowledge on the response to the initial smoke exposures might enhance the understanding of changes due to chronic smoking, since repetitive acute smoke effects may cumulate and lead to irreversible lung damage.

Methods: We investigated acute effects of smoking on inflammation in 16 healthy intermittent smokers in an open randomised cross-over study.

Development, validity and responsiveness of the Clinical COPD Questionnaire.

Background: The new Global Obstructive Lung Disease (GOLD) guidelines advice to focus treatment in Chronic Obstructive Pulmonary Disease (COPD) on improvement of functional state, prevention of disease progression and minimization of symptoms. So far no validated questionnaires are available to measure symptom and functional state in daily clinical practice. The aim of this study was to develop and validate the Clinical COPD Questionnaire (CCQ).