Expert Perspectives on the Management of Alpha 1-Antitrypsin Deficiency.

Alpha 1-antitrypsin deficiency is an inherited autosomal codominant disorder, which predisposes patients to lung and/or liver disease. Even though it is considered rare, it is one of the most frequent genetic disorders worldwide, albeit remaining underdiagnosed. Several organizations and societies, including the Portuguese Society of Pulmonology have been elaborating guidelines and recommendations for the diagnosis and management of alpha 1-antitrypsin deficiency. Nevertheless, some important matters are yet to be included in those, mainly due to lack of robust scientific evidence, and continue to represent a point of discussion. This article reviews some important scientific publications and expresses the perspectives of a group of Portuguese experts regarding the management of alpha 1-antitrypsin deficiency, namely in terms of the pre and neonatal diagnosis, the impact of the COVID-19 pandemic, the validity of replacement therapy in lung transplant-receiving, and finally, alternative strategies of alpha 1-antitrypsin deficiency treatment to improve the patients' quality of life.

A deficiência de alfa 1-antitripsina é uma doença hereditária autossómica codominante que aumenta a predisposição para o desenvolvimento de doença pulmonar e/ou hepática. Esta doença, embora seja considerada rara, é um dos distúrbios genéticos mais comuns em todo o mundo. Contudo, atualmente ainda constitui uma doença subdiagnosticada. Várias organizações e sociedades, incluindo a Sociedade Portuguesa de Pneumologia, elaboraram recomendações e diretrizes para o diagnóstico e gestão da deficiência de alfa 1-antitripsina. Porém, estes documentos ainda não abordam alguns temas relevantes associados à gestão da deficiência de alfa 1-antitripsina, principalmente devido à falta de robustez na evidência científica, que continuam a representar um ponto de discussão entre a comunidade médica. Neste artigo é feita a revisão de publicações científicas relevantes acerca da deficiência de alfa 1-antitripsina, e são descritas as perspetivas de especialistas portugueses sobre a gestão da deficiência de alfa 1-antitripsina, nomeadamente ao nível do diagnóstico pré e neonatal, do impacto da pandemia COVID-19, da validação da terapêutica de aumento em doentes que receberam um transplante pulmonar e, por fim, estratégias alternativas para a melhoria do tratamento da deficiência de alfa 1-antitripsina de modo a promover a qualidade de vida dos doentes.

A persistent wheeze.

What is the diagnosis of this woman with multiple respiratory infections in the previous year and a recent onset of progressive dyspnoea and wheezing? https://bit.ly/3bLgw2A.

The role of sleepiness on arterial stiffness improvement after CPAP therapy in males with obstructive sleep apnea: a prospective cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased cardiovascular risk. This study aim to assess differences in changes in arterial stiffness of two groups of patients, defined as having daytime sleepiness or not, after continuous positive airway pressure (CPAP) treatment. METHODS: A selected cohort of consecutive male patients, under 65 years old, with moderate to severe OSA and without great number of comorbidities was studied. The diagnosis was confirmed by home respiratory poligraphy. Sleepiness was considered with an Epworth Sleepiness Scale (ESS) > 10. An ambulatory blood pressure (BP) monitoring and carotid-femoral pulse wave velocity (cf-PWV) measurements were performed, before and after four months under CPAP. Compliant patients, sleepy and non-sleepy, were compared using linear mixed effects regression models. A further stratified analysis was performed with non-sleepy patients. RESULTS: Thirty-four patients were recruited, with mean age 55.2 (7.9) years, 38.2% were sleepy, 79.4% with hypertension, 61.8% with metabolic syndrome and 82.4% with dyslipidaemia. In univariable analysis, cf-PWV was strongly related to systolic BP parameters and age, but also to antihypertensive drugs (p = 0.030), metabolic syndrome (p = 0.025) and daytime sleepiness (p = 0.004). Sleepy patients had a more severe OSA, with AHI 44.8 (19.0) vs 29.7 (15.7) events/h (p = 0.018), but sleep study parameters were not associated with cf-PWV values. On multivariable regression, a significant interaction between time (CPAP) and sleepiness (p = 0.033) was found. There was a weak evidence of a cf-PWV reduction after CPAP treatment (p = 0.086), but the effects of treatment differed significantly between groups, with no changes in non-sleepy patients, while in sleepy patients a significant decrease was observed (p = 0.012). Evaluating non-sleepy patients group under CPAP therapy, results showed that both higher pulse pressure (p = 0.001) and lower LDL-cholesterol levels (p = 0.015) at baseline were associated to higher cf-PWV changes. CONCLUSIONS: Patients with daytime sleepiness had a more severe OSA and presented a greater arterial stiffness improvement after CPAP therapy, independently from age and BP. Besides sleepiness, cf-PWV reduction after CPAP therapy was mainly associated to CV risk factors, and less to sleep study parameters. TRIAL REGISTRATION: Clinicaltrials.gov NCT02273089 23.10.2014 retrospectively registered.

Use of CPAP to reduce arterial stiffness in moderate-to-severe obstructive sleep apnoea, without excessive daytime sleepiness (STIFFSLEEP): an observational cohort study protocol.

INTRODUCTION: Sleepiness is a cardinal symptom in obstructive sleep apnoea (OSA) but most patients have unspecific symptoms. Arterial stiffness, evaluated by pulse wave velocity (PWV), is related to atherosclerosis and cardiovascular (CV) risk. Arterial stiffness was reported to be higher in patients with OSA, improving after treatment with continuous positive airway pressure (CPAP). This study aims to assess whether the same effect occurs in patients with OSA and without sleepiness. METHODS AND ANALYSIS: This observational study assesses the CV effect of CPAP therapy on a cohort of patients with moderate-to-severe OSA; the effect on the subcohorts of sleepy and non-sleepy patients will be compared. A systematic and consecutive sample of patients advised CPAP therapy will be recruited from a single outpatient sleep clinic (Centro Hospitalar de Lisboa Central-CHLC, Portugal). Eligible patients are male, younger than 65 years, with confirmed moderate-to-severe OSA and apnoea-hypopnea index (AHI) above 15/hour. Other sleep disorders, diabetes or any CV disease other than hypertension are exclusion criteria. Clinical evaluation at baseline includes Epworth Sleepiness Scale (ESS), and sleepiness is defined as ESS above 10. OSA will be confirmed by polygraphic study (cardiorespiratory, level 3). Participants are advised to undertake an assessment of carotid-femoral PWV (cf-PWV) and 24 hours evaluation of ambulatory blood pressure monitoring (ABPM), at baseline and after 4 months of CPAP therapy. Compliance and effectiveness of CPAP will be assessed. The main outcome is the variation of cf-PWV over time. ETHICS AND DISSEMINATION: This protocol was approved by the Ethics Committees of CHLC (reference number 84/2012) and NOVA Medical School (number36/2014/CEFCM), Lisbon. Informed, written consent will be obtained. Its results will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02273089; Pre-results.