Mutations that permit residual CFTR function delay acquisition of multiple respiratory pathogens in CF patients

<p>Abstract</p> <p>Background</p> <p>Lung infection by various organisms is a characteristic feature of cystic fibrosis (CF). <it>CFTR </it>genotype effects acquisition of <it>Pseudomonas aeruginosa (Pa)</it>, however the effect on acquisition of other infectious organisms that frequently precede <it>Pa </it>is relatively unknown. Understanding the role of CFTR in the acquisition of organisms first detected in patients may help guide symptomatic and molecular-based treatment for CF.</p> <p>Methods</p> <p>Lung infection, defined as a single positive respiratory tract culture, was assessed for 13 organisms in 1,381 individuals with CF. Subjects were divided by predicted CFTR function: 'Residual': carrying at least one partial function <it>CFTR </it>mutation (class IV or V) and 'Minimal' those who do not carry a partial function mutation. Kaplan-Meier estimates were created to assess <it>CFTR </it>effect on age of acquisition for each organism. Cox proportional hazard models were performed to control for possible cofactors. A separate Cox regression was used to determine whether defining infection with <it>Pa</it>, mucoid <it>Pa </it>or <it>Aspergillus (Asp) </it>using alternative criteria affected the results. The influence of severity of lung disease at the time of acquisition was evaluated using stratified Cox regression methods by lung disease categories.</p> <p>Results</p> <p>Subjects with 'Minimal' CFTR function had a higher hazard than patients with 'Residual' function for acquisition of 9 of 13 organisms studied (HR ranging from 1.7 to 3.78 based on the organism studied). Subjects with minimal CFTR function acquired infection at a younger age than those with residual function for 12 of 13 organisms (p-values ranging: < 0.001 to 0.017). Minimal CFTR function also associated with younger age of infection when 3 alternative definitions of infection with <it>Pa</it>, mucoid <it>Pa </it>or <it>Asp </it>were employed. Risk of infection is correlated with CFTR function for 8 of 9 organisms in patients with good lung function (>90%ile) but only 1 of 9 organisms in those with poorer lung function (<50%ile).</p> <p>Conclusions</p> <p>Residual CFTR function correlates with later onset of respiratory tract infection by a wide spectrum of organisms frequently cultured from CF patients. The protective effect conferred by residual CFTR function is diminished in CF patients with more advanced lung disease.</p

Dual-source CT for chest pain assessment

Comprehensive CT angiography protocols offering a simultaneous evaluation of pulmonary embolism, coronary stenoses and aortic disease are gaining attractiveness with recent CT technology. The aim of this study was to assess the diagnostic accuracy of a specific dual-source CT protocol for chest pain assessment. One hundred nine patients suffering from acute chest pain were examined on a dual-source CT scanner with ECG gating at a temporal resolution of 83 ms using a body-weight-adapted contrast material injection regimen. The images were evaluated for the cause of chest pain, and the coronary findings were correlated to invasive coronary angiography in 29 patients (27%). The files of patients with negative CT examinations were reviewed for further diagnoses. Technical limitations were insufficient contrast opacification in six and artifacts from respiration in three patients. The most frequent diagnoses were coronary stenoses, valvular and myocardial disease, pulmonary embolism, aortic aneurysm and dissection. Overall sensitivity for the identification of the cause of chest pain was 98%. Correlation to invasive coronary angiography showed 100% sensitivity and negative predictive value for coronary stenoses. Dual-source CT offers a comprehensive, robust and fast chest pain assessment