Utility of routine screening for alpha-1 antitrypsin deficiency in patients with bronchiectasis.

Alpha-1 antitrypsin deficiency (AATD) is a cause of bronchiectasis. Guidelines for bronchiectasis from the British Thoracic Society do not recommend to routinely test patients for AATD. In contrast, guidelines for AATD recommend routine screening. This contradiction, in part, results from the lack of data from large studies performing comprehensive screening. We screened 1600 patients with bronchiectasis at two centres in the UK from 2012 to 2016. In total, only eight individuals with AATD were identified representing 0.5% of the overall population. We conclude that routine screening for AATD in bronchiectasis in the UK has a low rate of detection. Further studies are required in different geographical regions, which may have a higher prevalence of AATD.

Lung Adenocarcinoma Presenting as a Multiple Cavitary Disease / Adenocarcinoma pulmonar que se presenta como una enfermedad cavitada múltiple

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A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation.

INTRODUCTION: Neutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick - NEATstik®) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk. METHODS: Sputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik®, which scores neutrophil elastase concentration from 0 (<8 µg·mL-1 elastase activity) to 10 (maximum detectable neutrophil elastase activity). High neutrophil elastase activity was regarded as a NEATstik® grade >6. Severity of disease, airway infection from sputum culture and exacerbations over the 12 months were recorded. An independent validation was conducted in 50 patients from Milan, Italy. MEASUREMENTS AND MAIN RESULTS: Patients had a median age of 69 years and forced expiratory volume in 1 s (FEV1) 69%. High neutrophil elastase activity was associated with worse bronchiectasis severity using the bronchiectasis severity index (p=0.0007) and FEV1 (p=0.02). A high NEATstik® grade was associated with a significant increase in exacerbation frequency, incident rate ratio 2.75 (95% CI 1.63-4.64, p<0.001). The median time to next exacerbation for patients with a NEATstik® grade >6 was 103 days compared to 278 days. The hazard ratio was 2.59 (95% CI 1.71-3.94, p<0.001). Results were confirmed in the independent validation cohort. CONCLUSIONS: A novel lateral flow device provides assessment of neutrophil elastase activity from sputum in minutes and identifies patients at increasing risk of airway infection and future exacerbations.

Interstitial Lung Disease Induced by Crizotinib in Non-Small-Cell Lung Cancer.

The treatment of advanced non-small-cell lung cancer shifted with the development of molecular-targeted therapies, like the tyrosine kinase inhibitors. One example of tyrosine kinase inhibitors is crizotinib, an anaplastic lymphoma tyrosine kinase inhibitor, which targets an echinoderm microtubule-associated protein-like-4-anaplastic lymphoma kinase gene fusion. This mutation is found in only 2% to 7% of non-small-cell lung cancer cases. Although these new therapies have shown promising results, the occurrence of interstitial lung disease as a side effect could be problematic. As the diagnosis of drug-related-interstitial lung disease is difficult to make, computed tomography is an important diagnostic tool. The recognition of computed tomography manifestations of tyrosine kinase inhibitors -induced interstitial lung disease is the key for an early recognition and management of this pulmonary toxicity. We aim to raise awareness of tyrosine kinase inhibitors-induced interstitial lung disease, by reporting the first case of a Portuguese patient treated with crizotinib for non-small-cell lung cancer who developed drug-induced interstitial lung disease.

O tratamento do carcinoma do pulmão de não pequenas células avançado mudou com o desenvolvimento de novas terapêuticas moleculares, tais como os inibidores da tirosina quinase. Um destes exemplos é o crizotinib que tem como alvo inibir a translocação do gene da quinase do linfoma, que se encontra presente em 2% a 7% dos casos de carcinoma do pulmão de não pequenas células. Apesar destes novos tratamentos mostrarem resultados promissores, a ocorrência de doença pulmonar intersticial como efeito secundário pode ser problemática. O diagnóstico de doença pulmonar intersticial associada ao tratamento é de difícil confirmação, o que tornou a tomografia computorizada uma importante ferramenta no diagnóstico. Pretendemos alertar para a doença pulmonar intersticial relacionada com os inibidores da tirosina quinase através da apresentação do primeiro caso de uma doente portuguesa tratada com crizotinib para carcinoma do pulmão de não pequenas células que desenvolveu doença pulmonar intersticial.