Perspectivas atuais sobre inflamação e remodelamento das vias aéreas na asma e na rinite alérgica / Current perspectives on airway inflammation and remodelling in asthma and allergic rhinitis

O desenvolvimento da rinite alérgica (RA) e da asma requer uma interação entre ambiente, sistema imunológico e susceptibilidade genética. Enquanto a rinite induzida por pólen é a mais característica doença alérgica mediada pela imunoglobulina E, na RA perene os desencadeantes da alergia são mais contínuos e levam à inflamação constante. Várias células e mediadores coordenam e mantêm essa inflamação. Embora a histamina ainda seja um dos principais mediadores da reação alérgica, muitos outros mediadores produzidos por diferentes tipos celulares estão envolvidos. Assim, a intrincada interação entre esses mediadores, citocinas, quimiocinas, neuropeptídeos, moléculas de adesão e várias células na forma de uma rede complexa leva ao desenvolvimento de sintomas específicos e à hiper-reatividade não específica presente na RA. A asma é caracterizada por graus variáveis de inflamação crônica e alterações estruturais nas vias aéreas que incluem denudação epitelial, metaplasia das células caliciformes, espessamento subepitelial, aumento da massa do músculo liso nas vias aéreas, aumento das glândulas brônquicas, angiogênese, e alterações nos componentes da matriz extracelular envolvendo as pequenas e grandes vias aéreas. Acredita-se que a inflamação crônica inicie e perpetue ciclos de dano e reparo tecidual na asma, embora o remodelamento também possa ocorrer em paralelo com a inflamação. Ao mesmo tempo em que RA e asma apresentam várias semelhanças em termos de perfil e resposta das células inflamatórias e dos mediadores, o remodelamento como observado na asma não é característico da RA. Na asma, as relações entre inflamação e remodelamento das vias aéreas e função pulmonar estão sendo melhor compreendidas. Uma variedade de células inflamatórias e células estruturais atuam na coordenação da inflamação e das mudanças estruturais na asma. O aumento da responsividade das vias aéreas é um marcador substituto de inflamação e pode refletir o desenvolvimento de mudanças estruturais nas vias aéreas. Tal aumento persistente da responsividade brônquica aponta para a ocorrência de remodelamento parcialmente resistente à terapia.

The development of AR and asthma requires an interaction between the environment, imune system and genetic susceptibility. While pollen-induced rhinitis is the most characteristic IgE mediated allergic disease, in perennial allergic rhinitis the allergic triggers are more continuous, and lead to on going inflammation. Several cells and mediators orchestrate and maintain this inflammation. Although histamine is still one of the major mediators of the allergic reaction, many other mediators produced by different cell types are involved. Thus, the intricate interaction amongst these mediators, cytokines, chemokines, neuropeptides, adhesion molecules and various cells in the form of a complex network leads to the development of specific symptoms and the non specific hyperreactivity of allergic rhinitis. Asthma is characterized by variable degrees of chronic inflammation and structural alterations in the airways which include epithelial denudation, goblet cell metaplasia, subepithelial thickening, increased airway smooth muscle mass, bronchial gland enlargement, angiogenesis, and alterations in extracellular matrix components, involving large and small airways. Chronic inflammation is thought to initiate and perpetuate cycles of tissue injury and repair in asthma, although remodeling may also occur in parallel with inflammation. While AR and asthma share several similarities in the inflammatory cell and mediator profiles and responses, remodeling as seen in asthma is not characteristic of AR. In asthma, the relationships of airway inflammation, remodeling and lung function are becoming better understood. A variety of inflammatory cells and structural cells play a role in orchestrating the inflammation and structural changes in asthma. Increased airway responsiveness is a surrogate marker of inflammation and may reflect the development of structural changes in the airways. Such persistent increased bronchial responsiveness indicates remodeling which is partly resistant to therapy.

Allergic rhinitis and its impact on asthma update (ARIA 2008) - western and asian-pacific perspective.

The prevalence of allergic diseases such as allergic rhinitis (AR) and asthma is markedly increasing worldwide as societies adopt western life styles. Allergic sensitization is an important risk factor for asthma and AR, and asthma often co-exists with AR. An estimated 300 million people worldwide have asthma, about 50% of whom live in developing countries and about 400 million people suffer from AR. Yet, AR is often under-diagnosed and under-treated due to a lack of appreciation of the disease burden and its impact on quality of life, as well as its social impact at school and at the workplace. However, AR with or without asthma is a huge economic burden. Thus, there was clearly a need for a global evidence-based document which would highlight the interactions between the upper and lower airways including diagnosis, epidemiology, common risk factors, management and prevention. The Allergic Rhinitis and its Impact on Asthma (ARIA) document was first published in 2001 as a state-of-the-art guide-line for the specialist, the general practitioner and other health care professionals. Subsequent new evidence re-garding the pathomechanisms, new drugs and increased knowledge have resulted in the publication of the ARIA 2008 update. The present review summarizes the ARIA update with particular emphasis on the current status of AR and asthma in the Asia-Pacific region and discusses the Western and Asian perspective

Allergic rhinitis and co-morbid asthma: Perspective from India- ARIA Asia-Pacific Workshop Report.

In India, allergic rhinitis (AR) is considered to be a trivial disease, despite the fact that symptoms of rhinitis were present in 75% of children and 80% of asthmatic adults. Traditionally, AR was also divided into sea-sonal or perennial, based on the time of occurrence of symptoms during the year. The ARIA workshop report pro-posed that patients be categorized as “intermittent” and “persistent” while severity was classified as “mild” and “moderate-severe”. Patients with AR, depending on their predominant symptom, can also be categorized as “sneezers-runners” and “blockers”. On sketching their clinical profile, it was observed that “blockers” had signifi-cantly higher sinusitis and had higher sensitization to fungi. Skin allergy testing in Indian adults showed that in pa-tients with AR house dust mite (Dermatophagoides farinae) was the most common allergen. Studies conducted in India have shown that AR often restricts the patient’s quality of life (QOL). It can affect the physical, psychological and social aspects of the patients’ life and can also impact their functions at work. Furthermore, AR adversely af-fects sleep related QOL. Topical corticosteroids are now considered as the cornerstone of the treatment for AR. In spite of causing a major impact on the QOL in Indian patients, AR is rarely given the importance it deserves.

Allergic rhinitis and asthma: from the link to emerging therapies.

Epidemiological evidences and clinical as well as experimental observations have suggested a link between rhinitis and asthma. This relationship between rhinitis (and sinusitis) and asthma also involve other aspects, such as viral infections and bronchial hyperreactivity. These have been further confirmed by functional and immunological evidences, challenge studies of the nose and the bronchii, and, indirectly, by observing the therapeutic effects of drugs used mainly for rhinitis on the symptoms of asthma. Therefore, the present article is a review of the most relevant experimental results, so far provided, supporting the 'One Airway One Disease' concept, the possible mechanisms involved in this link and emerging therapeutic strategies like leukotriene receptor antagonists.

Allergic rhinitis and its impact on asthma: an evidence-based treatment strategy for allergic rhinitis.

The overall pathogenic view of respiratory allergy has deeply changed and evolved during the last ten years. Much emphasis has been laid to the relationship between rhinitis and asthma, which is between the upper and the lower respiratory airways. This strict link has been evidenced through clinical observations and epidemiological studies and also on the basis of immunological observations and outcomes of therapy. Furthermore, the frequent co-existence of rhinitis and asthma (up to 80 percent of asthmatic patients have co-existing allergic rhinitis, while up to 40 percent of allergic rhinitis patients have asthma, the coexistence of sinusitis and asthma, the presence of rhinitis as a risk factor for developing asthma, further emphasize this link and together lead to the operative definition of Allergic Rhinobronchitis or, United Airways Disease (UAD). The strict link existing between upper and lower respiratory tract can be also regarded from the viewpoint of therapeutical outcomes. The more detailed knowledge of the intricate mechanisms sustaining allergic inflammation in the respiratory tract (i.e. antigen presentation, cytokines, chemokines and adhesion molecules) has clarified the functional relationships between nose and lung. Thus allergic rhinitis or asthma is not a disease confined to a specific target organ, but rather a disorder of the whole respiratory tract, with a range of clinical manifestations, leading to relevant diagnostic and therapeutic implications as indicated in the WHO Initiative ARIA, the first evidence-based guideline emphasizing the impact of allergic rhinitis on asthma and where a step-wise treatment strategy targeting both the upper and lower airway effectively has been proposed. Moreover, the use of novel potential therapies that target both rhinitis and asthma like antileukotrienes or anti-IgE are indeed a future strategy.