Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy.

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case-control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T>G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A>G variant in the IL13RA1 proximal 3' untranslated region. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between the IL13RA1 -281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics. These findings indicate that the interleukin-13 receptor alpha1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor alpha1 subunit gene locus might be involved in the control of immunoglobulin E production.     

Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant.

Pulmonary hypertension (PH) may complicate idiopathic pulmonary fibrosis (IPF) but the prevalence of PH in IPF remains undefined. The present authors sought to describe the prevalence of PH in IPF. The lung transplant registry for the USA (January 1995 to June 2004) was analysed and IPF patients who had undergone right heart catheterisation (RHC) were identified. PH was defined as a mean pulmonary arterial pressure ((Ppa)) > or =25 mmHg and severe PH as a (Ppa) >40 mmHg. Independent factors associated with PH were determined. Of the 3,457 persons listed, 2,525 (73.0%) had undergone RHC. PH affected 46.1% of subjects; approximately 9% had severe PH. Variables independently associated with mild-to-moderate PH were as follows: need for oxygen, pulmonary capillary wedge pressure (P(pcw)) and forced expiratory volume in one second (FEV(1)). Independent factors related to severe PH included the following: carbon dioxide tension, age, FEV(1), P(pcw), need for oxygen and ethnicity. A sensitivity analysis in subjects with P(pcw) <15 mmHg did not appreciably alter the present findings. Pulmonary hypertension is common in idiopathic pulmonary fibrosis patients awaiting lung transplant, but the elevations in mean pulmonary arterial pressure are moderate. Lung volumes alone do not explain the pulmonary hypertension. Given the prevalence of pulmonary hypertension and its relationship with surrogate markers for quality of life (e.g. activities of daily living), future trials of therapies for this may be warranted.     

Definition, epidemiology and natural history of COPD.

Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for alpha(1)-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.     

Congenital dextrocardia complicated by hypertension,coronary artery disease and myocardial infarction

The case record of a seventy-three year old man with congenital dextrocardia and situs inversus viscerum complicated by hypertension, coronary artery disease and myocardial infarction is presented. Electrocardiographic recordings of the limb leads, with and without reversal of the arm lead wires, and of the precordial leads of the V series derived from both right and left chest areas are presented. In this instance the electrocardiographic findings in precordial leads taken over the right chest point to fresh anteroseptal infarction; those leads recorded from the left chest were not informative. This serves to emphasize the fact that precordial leads should be recorded from the right side of the chest rather than the left in order that the exploring precordial electrode may overlie the area of cardiac damage, and thus manifest maximal changes in the electrocardiogram. We agree that the electrocardiogram may best be interpreted by application of the usual criteria to the limb leads taken with the arm lead wires reversed although in this case the limb leads yielded no information of diagnostic significance.