Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)

Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.

The role of anaerobic bacteria in the cystic fibrosis airway

PURPOSE OF REVIEW: Anaerobic bacteria are not only normal commensals, but are also considered opportunistic pathogens and have been identified as persistent members of the lower airway community in people with cystic fibrosis of all ages and stages of disease. Currently, the role of anaerobic bacteria in cystic fibrosis lower airway disease is not well understood. Therefore, this review describes the recent studies relating to the potential pathophysiological role(s) of anaerobes within the cystic fibrosis lungs.

RECENT FINDINGS: The most frequently identified anaerobic bacteria in the lower airways are common to both cystic fibrosis and healthy lungs. Studies have shown that in cystic fibrosis, the relative abundance of anaerobes fluctuates in the lower airways with reduced lung function and increased inflammation associated with a decreased anaerobic load. However, anaerobes found within the lower airways also produce virulence factors, may cause a host inflammatory response and interact synergistically with recognized pathogens.

SUMMARY: Anaerobic bacteria are potentially members of the airway microbiota in health but could also contribute to the pathogenesis of lower airway disease in cystic fibrosis via both direct and indirect mechanisms. A personalized treatment strategy that maintains a normal microbial community may be possible in the future.

Asthma and rhinitis have different genetic profiles for IL13, IL17A and GSTP1 polymorphisms

BACKGROUND: Asthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds. PURPOSE: To evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry. METHODS: 192 unrelated healthy individuals and 232 patients, 83 with rhinitis and 149 with asthma, were studied. All polymorphisms were detected by real time polymerase chain reaction (PCR) using TaqMan assays. RESULTS: Comparing to controls, significant association with asthma was observed for GSTP1 rs1695 AA genotype (odds ratio (OR) - 1.96; 95% CI - 1.18 to 3.25; p=0.010). The association sustains for allergic asthma (OR - 2.17; 95% CI - 1.23 to 3.80; p=0.007). IL13 rs20541 GG genotype was associated with less susceptibility to asthma (OR - 0.55, 95% CI - 0.33 to 0.94, p=0.028). Among patients, IL17A rs2275913 AA genotype was less associated with asthma than with rhinitis (OR - 0.20; 95% CI of 0.07 to 0.56; p=0.002). A similar association was found for IL13 rs20541 GG genotype (OR - 0.48; 95% CI of 0.25 to 0.93; p=0.031). There were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls for the IL4R polymorphism' analyzed. CONCLUSION: These results support the existence of a significant association between GSTP1 rs1695 and IL13 rs20541 SNPs, with susceptibility to asthma, in the population studied. Different genotype profiles of IL17A and IL13 genes seem to influence the clinical pattern of disease expression mainly confined to the upper airways, as rhinitis, or including the lower airways, as asthma.

Phocid seal leptin: tertiary structure and hydrophobic receptor binding site preservation during distinct leptin gene evolution

The cytokine hormone leptin is a key signalling molecule in many pathways that control physiological functions. Although leptin demonstrates structural conservation in mammals, there is evidence of positive selection in primates, lagomorphs and chiropterans. We previously reported that the leptin genes of the grey and harbour seals (phocids) have significantly diverged from other mammals. Therefore we further investigated the diversification of leptin in phocids, other marine mammals and terrestrial taxa by sequencing the leptin genes of representative species. Phylogenetic reconstruction revealed that leptin diversification was pronounced within the phocid seals with a high dN/dS ratio of 2.8, indicating positive selection. We found significant evidence of positive selection along the branch leading to the phocids, within the phocid clade, but not over the dataset as a whole. Structural predictions indicate that the individual residues under selection are away from the leptin receptor (LEPR) binding site. Predictions of the surface electrostatic potential indicate that phocid seal leptin is notably different to other mammalian leptins, including the otariids. Cloning the grey seal leptin binding domain of LEPR confirmed that this was structurally conserved. These data, viewed in toto, support a hypothesis that phocid leptin divergence is unlikely to have arisen by random mutation. Based upon these phylogenetic and structural assessments, and considering the comparative physiology and varying life histories among species, we postulate that the unique phocid diving behaviour has produced this selection pressure. The Phocidae includes some of the deepest diving species, yet have the least modified lung structure to cope with pressure and volume changes experienced at depth. Therefore, greater surfactant production is required to facilitate rapid lung re-inflation upon surfacing, while maintaining patent airways. We suggest that this additional surfactant requirement is met by the leptin pulmonary surfactant production pathway which normally appears only to function in the mammalian foetus.

A Ortodontia e aparelhos intra orais no tratamento da SAHOS (Sindrome da Apneia e Hipopneia Obstrutiva do Sono)

A síndrome da apneia e hipopneia obstrutiva do sono (SAHOS) é uma patologia que atinge cerca de 4% da população adulta, é uma doença crónica, progressiva, com alta morbilidade e mortalidade. A apneia do sono e o ronco têm despertado a atenção da área da saúde devido às inúmeras comorbilidades associadas. Esta síndrome é caracterizada por obstrução parcial ou total das vias aéreas superiores durante o sono e manifesta-se como uma redução (hipopneia) ou cessação (apneia) do fluxo aéreo. A queixa habitual dos pacientes além dos problemas sociais como ronco e a hipersonolência diurna, são a preocupação com outros quadros que esta patologia pode desencadear, como insuficiência cardíaca e hipertensão pulmonar. O tratamento da apneia obstrutiva do sono é multidisciplinar e indispensável, podendo ser realizado de diversas formas, tanto conservadoras como cirúrgicas, dependendo de inúmeros fatores como a gravidade da doença, as alterações anatómicas das vias aéreas superiores, idade e condições sistémicas do paciente. Os aparelhos intra orais têm sido usados durante anos, no tratamento da SAHOS como controle da obstrução das vias aéreas superiores. A terapia com aparelhos intraorais é simples e reversível. O sucesso do tratamento com aparelhos intra orais para o ronco e SAHOS leve e moderada é comprovado pela grande maioria dos estudos. A facilidade de uso, manutenção e conforto quando comparados a outros tratamentos faz com que os aparelhos intrabucais sejam considerados de fácil aceitação pelos pacientes. Através de uma revisão de literatura discutiu-se o uso de aparelhos intrabucais para o tratamento dessa patologia, destacando a eficácia e as limitações dessa terapia, os principais sintomas clínicos, os principais efeitos colaterais oclusais, o grau de colaboração e o índice de satisfação dos pacientes. Foi possível concluir que aparelhos intrabucais de avanço mandibular estão amplamente indicados para o tratamento do ronco e da SAHOS como terapia principal, ou alternativa naqueles pacientes que não podem suportar a terapia da pressão positiva das vias aéreas e que para o sucesso do tratamento é fundamental uma equipe multidisciplinar, incluindo um Médico Dentista e a colaboração do paciente.

A utilização das análises cefalométricas no diagnóstico dos distúrbios do sono

A Síndrome da Apneia e Hipopneia Obstrutiva do Sono (SAHOS) é uma doença crónica, de carácter progressivo, que atinge cerca de 4% da população adulta. A obstrução parcial ou total das vias aéreas superiores durante o sono pode provocar quadros de hipopneia (uma redução do fluxo aéreo) ou apneia (cessação completa do fluxo aéreo). Os pacientes queixam-se de sonolência diurna excessiva, ronco durante a noite e além destes problemas sociais a preocupação pela redução de funções cognitivas que se podem desencadear, como memória, atenção, hipertensão pulmonar e insuficiência cardíaca. O Médico Dentista está habilitado para avaliar o espaço aéreo oro e nasofaringeo e diagnosticar, além da necessidade de correções dentárias, a presença de obstruções das Vias Aereas Superiores (VAS) orientando assim o seu tratamento. Além do exame clínico, o diagnóstico de distúrbios respiratórios do sono é baseado na história clínica, exame físico e confirmado através da polissonografia e da análise cefalométrica. Esta tem sido considerada como um método importante no diagnóstico, fornecendo características craniofaciais que permitem verificar a existência de pré-disposição de SAHOS. As avaliações com cefalometrias obtidas em telerradiografias em norma lateral é um recurso essencial para realizar o diagnóstico de distúrbios respiratórios do sono, desde que o profissional tenha domínio da técnica e da sua interpretação. Estes distúrbios são caracterizados por diferentes graus de diminuição do espaço das vias aéreas superiores, causado por factores anatómicos e funcionais, que podem ser analisados pelo profissional. A intervenção precoce torna-se crucial, pela diminuição da morbilidade, melhores resultados no tratamento, diminuição de gastos nos serviços de saúde e melhor qualidade de vida do paciente. O presente trabalho teve por objectivo realizar uma revisão bibliográfica sobre a importância da avaliação das vias aéreas superiores através da análise de grandezas cefalométricas obtidas de telerradiografias em norma lateral como padrão de diagnóstico para a identificação de distúrbios respiratórios do sono.

Professional exposure to fungal pathogens: an update to exposure conditions and exposure measurement

In many occupational settings an exposure to fungi occurs. Fungal exposure may occur for instance in the form of dermatocytes, yeasts or mold. Associated to the fungi themselves an exposure to cell wall components like ß(1 ? 3)-D-glucans, to mycotoxins or to microbial volatile compounds can occur. Health hazards may differ across species because fungi may produce different allergens and mycotoxins, and some species can infect humans. Occupational settings are often characterized by special exposure conditions with respect to duration, frequency and especially to the level of exposure resulting at least sometimes to high or very high fungal exposure. Because of these special conditions occupational settings are suitable for epidemiologic studies. However, the knowledge about occupational exposure to fungi and associated compounds like mycotoxins is still fragmentary and not well disseminated. An indication for a high fungal exposure is for instance the handling of dry natural products like grain, hay or herbal plants with a high specific surface and the tendency to release dust during handling. The fungal components often form the determinative part of such dusts and might be a vehicle to respiratory airways. The authors will present results of exposure measurements of occupational settings and exposure conditions which are only rarely investigated.

An Unusual Case of Cerebral Oedema

Hereditary angioedema (HAE) is a rare genetic disorder transmitted as an autosomal dominant trait, characterized by reduced plasma concentration or by the presence of non-functional C1 esterase inhibitor. Oedema caused by HAE mostly affects the skin and bowel and can induce swelling of genitalia. Oedema can be life threatening if it causes swelling of the larynx with obstruction of the airways. We describe the case of a 52-year-old man who presented a neurological emergency (coma), where the remarkable localization of the clinical manifestation and the unusual symptomatology hindered the correct diagnosis.

Severe Acute Dyspnoea of Extra-Thoracic Origin: Experience with Three Primary Thyroid Lymphomas (PTL)

Objectives: To recall the common clinical presenting features of and guide the diagnostic procedures of primary thyroid lymphomas (PTL). Materials and methods: We report on three patients developing an acute dyspnoea and fast evolving neck mass in the thyroid caused by a PTL occurring in our regional hospital in Switzerland between 2009 and 2013. Results: PTL causes a neck mass, dyspnoea and dysphonia and responds well to chemotherapy. Mortality is due to relapse or infectious complications. Conclusion: Acute dyspnoea caused by thyroid disease is uncommon. Nevertheless, it is the main symptom in PTL due to rapid growth and compression of the airways. Chemotherapy should be started promptly.

Asthma and rhinitis have different genetic profiles for IL13, IL17A and GSTP1 polymorphisms

BACKGROUND: Asthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds. PURPOSE: To evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry. METHODS: 192 unrelated healthy individuals and 232 patients, 83 with rhinitis and 149 with asthma, were studied. All polymorphisms were detected by real time polymerase chain reaction (PCR) using TaqMan assays. RESULTS: Comparing to controls, significant association with asthma was observed for GSTP1 rs1695 AA genotype (odds ratio (OR) - 1.96; 95% CI - 1.18 to 3.25; p=0.010). The association sustains for allergic asthma (OR - 2.17; 95% CI - 1.23 to 3.80; p=0.007). IL13 rs20541 GG genotype was associated with less susceptibility to asthma (OR - 0.55, 95% CI - 0.33 to 0.94, p=0.028). Among patients, IL17A rs2275913 AA genotype was less associated with asthma than with rhinitis (OR - 0.20; 95% CI of 0.07 to 0.56; p=0.002). A similar association was found for IL13 rs20541 GG genotype (OR - 0.48; 95% CI of 0.25 to 0.93; p=0.031). There were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls for the IL4R polymorphism' analyzed. CONCLUSION: These results support the existence of a significant association between GSTP1 rs1695 and IL13 rs20541 SNPs, with susceptibility to asthma, in the population studied. Different genotype profiles of IL17A and IL13 genes seem to influence the clinical pattern of disease expression mainly confined to the upper airways, as rhinitis, or including the lower airways, as asthma.

Helicopter route chart, New York.

Aeronautical chart showing designated helicopter routes and control areas.

Flexible bronchoscopy contribution in the approach of diagnosis and treatment of children’s respiratory diseases: the experience of a unique pediatric unit in Tunisia.

Objective: Our study aimed at assessing the role of flexible bronchoscopy (FB) in improving diagnosis and management of children’s respiratory conditions in the pediatric unit of FB, newly created and unique in Tunisia. Methods: Retrospective study including all the FB achieved in our pediatric unit from 2009 to 2014. Results: We performed 365 FB in 333 patients aged 46 months on average (1 month - 15 years), often under conscious anesthesia (81.6%). FB was performed for diagnostic purposes in 341 cases and for therapeutic purposes in 24 cases. Eight anatomical abnormalities were revealed in 22 patients. An intraluminal bronchial obstruction was found in 71 FB, mainly due to a foreign body (n=36). A vascular anomaly was responsible for nine cases out of 17 extraluminal obstructions. Airways malacia was observed in 60 FB. Bronchoalveolar lavage was performed in 196 cases. It was determinant in 43.9% of the cases. FB was of great diagnostic value in 74.8% of the cases. It influenced the management of the patients in 58% of the cases. The FB for therapeutic purposes was beneficial in all cases. Few complications occurred (5.5%). Conclusion: FB is a safe tool providing precious diagnostic and/or therapeutic help for the clinician. Keywords:

Portugal at the cross road of international chronic respiratory programmes

July 1-4, 2015 two meetings will be held with the Directorate General of Health in Lisbon, Portugal to discuss chronic respiratory programmes of the WHO Global Alliance against Chronic Respiratory Diseases (GARD)1,2 and European Innovation Partnership on Active and Healthy Ageing (EIP on AHA)3 (AIRWAYS ICPs: Integrated Care Pathways for airway diseases).4 The goals of these meetings will be to make an update of these two international actions and to strengthen the WHO noncommunicable disease (NCD) action plan (2013---2020).

Estudo retrospetivo sobre traqueostomia permanente como tratamento cirúrgico em cães com síndrome braquicefálica obstrutiva

Dissertação de Mestrado Integrado em Medicina Veterinária

Investigation of the enhanced antimicrobial activity of combination dry powder inhaler formulations of lactoferrin

The airways of most people with cystic fibrosis are colonized with biofilms of the Gram-negative, opportunistic pathogen Pseudomonas aeruginosa. Delivery of antibiotics directly to the lung in the form of dry powder aerosols offers the potential to achieve high local concentrations directly to the biofilms. Unfortunately, current aerosolised antibiotic regimes are unable to efficiently eradicate these biofilms from the airways. We investigated the ability of the innate antimicrobial, lactoferrin, to enhance the activity of two aminoglycoside antibiotics (tobramycin and gentamicin) against biofilms of P. aeruginosa strain PAO1. Biofilms were prepared in 96 well polystyrene plates. Combinations of the antibiotics and various lactoferrin preparations were spray dried. The bacterial cell viability of the various spray dried combinations was determined. Iron-free lactoferrin (apo lactoferrin) induced a 3-log reduction in the killing of planktonic cell by the aminoglycoside antibiotics (p < 0.01) and also reduced both the formation and persistence of P. aeruginosa biofilms (p < 0.01). Combinations of lactoferrin and an aminoglycoside displays potential as an effective new therapeutic strategy in the treatment of P. aeruginosa biofilms infections such as those typical of the CF lungs.