Studies on the prevalence of allergic traits in relation to family history demonstrated incremental increases in risk of developing asthma or AR with the presence of one or both parents with allergic disease, and greater than three times the risk if allergic disease occurred in more than one first degree relative To date, a positive family history remains one of the most reliable tools for prognosis of allergic disease Moreover, the Multicentre Allergy Study has demonstrated that having parents with allergies is not only a strong predictor to develop any allergy but also strongly increases the risk of developing allergic multi-morbidity A link of asthma and AR with different chromosomal regions was recently found thanks to genome-wide association studies.
Actually, there are about different potential biomarkers involved in respiratory inflammation For example, Liu et al. The genetic studies of allergic disease pave the way for tailored treatments to specific genotypes to improve therapeutic outcomes and minimize side effects. Environmental exposures during pregnancy including diet, nutrient intake especially vitamin D 31 , toxins smoking, air pollution, microbes, infection can alter the epigenome and interact with inherited genetic and epigenetic risk factors to directly and indirectly influence organ development and immune programming Considering these data, the primary prevention of allergic disease should begin very early in life, even in utero Microbiome is the totality of microbes, their genes, and their interactions in a given environment.
It is increasingly accepted that human microbiome may play an important role by promoting the maturation of the host immune system. Thanks to advances in sequencing technologies, such as real-time quantitative PCR, it is now known that the microbes that inhabit healthy and diseased nose and lungs are different As matter of fact, children being raised on traditional farms have a much lower prevalence of allergic disease as children grown up in urban settings.
The diversity of the microbial exposure has been shown to account for the asthma-protective farm effect. Nevertheless, in urban areas high exposure to environmental microbes also relates to a lower prevalence of allergic disease 15 , So, the microbiome itself could be considered as a potential biomarker source.
The linking of asthma and Moraxella , however, was restricted to children not living on farms. In contrast to the nasal samples, the throat microbiota characteristics were not related to asthma Circulating miRNAs have been considered to be involved in many inflammatory diseases, although gene regulation in the common inflammatory processes in UAD remains unclear Panganiban et al.
These miRNAs fit into five different expression pattern groups. Among asthmatic patients, miRNA expression profiles identified two subtypes that differed by high or low peripheral eosinophil levels. Circulating miRb, miR, miRp, miR, miR, and miRb levels were most predictive of allergic and asthmatic status Interestingly, recent studies have shown that miRNAs could be used as potential pharmaceutical targets for anti-inflammatory treatment The interaction between nose and lung in allergic airways disease is a bidirectional process, indeed it has been proved that the treatment of AR can improve asthma symptoms 15 , Subsequent ARIA updates and other reviews have made an attempt to summarize the diagnostic and therapeutic implications of this link based on these published evidence, but the evidence is still far from conclusive, due to limited number of randomized controlled trials available on subjects with concomitant AR and asthma 15 , Therapy for UAD is based on avoidance of the main allergens and irritants and pharmacotherapy [nasal and inhaled steroids, antihistamines, leukotriene receptor antagonists LTRA , anti-IgE therapy, and allergen immunotherapy AIT ] Once allergy testing is complete, the physician may devise a comprehensive program of allergen avoidance.
The lack of hay fever outside the pollen season indicates that complete allergen avoidance can be effective. Unfortunately, complete avoidance is rarely possible, especially for outdoor allergens. The effects of environmental control strategies have been most heavily studied with regard to dust mites and furry pets Compliance with these measures may be difficult but will certainly be helpful in many patients with hypersensitivity to these allergens.
Avoidance of other rhinitis and asthma triggers, such as cigarette smoke, outdoor pollutants, fumes, and irritants, is sensible in clinical practice Some authors reported a decrease in asthma symptoms and AR after intranasal corticosteroid treatment of rhinitis and a recent meta-analysis confirmed the beneficial effect of intranasal steroids in AR Leukotrienes are generated by the metabolism of arachidonic acid via the 5-lipoxygenase 5-LO pathway, which is involved in the rapid initial inflammation response.
LTRAs block the cysteinyl-leukotriene receptor, which are peptide-conjugated lipids produced by activated basophils, eosinophils, mast cells, and macrophages, to relieve the symptom of AR The recombinant, humanized, monoclonal anti-IgE antibody Omalizumab forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation Omalizumab has been tested in several clinical trials, and its beneficial effect has been established in patients with uncontrolled allergic asthma, leading to its approval by FDA In patients with severe asthma and rhinitis, omalizumab improved nasal and bronchial symptoms and reduced unscheduled visits due to asthma.
The clinical benefit of treatment with omalizumab is associated with an anti-inflammatory effect on cellular markers in blood and nasal tissue, as well as with a reduction in FcRI expression and function The only treatment potentially able to interfere with the natural history of respiratory allergy is AIT, specifically aimed at modifying the response to sensitizing allergens In particular, AIT may prevent the onset of asthma by halting the progression from rhinitis, by preventing new sensitizations or by avoiding the primary development of allergy The link between upper and lower airways, the so-called UAD, has been revealed by several epidemiologic, pathophysiologic, and clinical evidences, changing the global pathogenic view of respiratory allergy.
AR and asthma are both manifestations of a single inflammatory process and require an integrated diagnostic and therapeutic approach in order to get global disease control. All authors made substantial contribution to the conception of the work, reviewed the literature on the subject, and drafted the final version of the manuscript; AL and GM revised it critically for important intellectual content.
All authors finally approved the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
The authors declare that written informed consent was obtained by the patients for the use of the images. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
United airway disease: current perspectives. J Asthma Allergy — Recent developments in united airways disease. Allergy Asthma Immunol Res —7. Allergy — Corren J. Allergic rhinitis and asthma: how important is the link? J Allergy Clin Immunol 99 2 :S—6. Sluder G. Asthma as a nasal reflex. JAMA 73 8 — Neurobiology of the upper and lower airways. Allergy 54 Suppl 57 — Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways.
J Allergy Clin Immunol 3 — Wang Y, Mccusker CT. Table 1 Airway hypersensitivity syndrome phenotypes. Rhinitis a 2. Rhinitis a with airway hyperresponsiveness 3. Eosinophilic bronchitis 4. Asthma 5. Rhinitis a and asthma. Open in a separate window. Note: a Rhinitis can be associated with conjunctivitis.
United airway disease: epidemiologic evidence AR is the most common of all atopic diseases, and although it can develop at any age, most patients report the onset of symptoms before 30 years of age, making it the most common chronic disorder in children. United airway disease: pathophysiological evidence The upper and lower respiratory tracts form a continuum, allowing the passage of air into and out of the lungs and sharing many anatomical and histological properties.
Figure 1. Air-conditioning Galen was the first to offer insights on the function of the nose as protector of the lower airway through its ability to clean, warm, and humidify inhaled air. Inflammation Propagation of inflammation from the upper airway to lower airway may occur via postnasal drip and systemic circulation.
Neural reflexes The existence of a nasobronchial reflex that originates from the sensory nerve endings in the nose, travels to the central nervous system through the trigeminal nerve, and follows an efferent pathway through the vagus nerve to produce airway smooth-muscle contraction has been under debate for years. United airway disease: clinical evidence There is also clinical evidence supporting the concept of UAD. Conclusion The treatment of rhinitis is indispensable in patients with asthma, since it leads to better control of both diseases, and the lessons of the ARIA initiative cannot be forgotten.
Footnotes Disclosure The authors report no conflicts of interest in this work. References 1. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. Nasobronchial interaction. World J Clin Cases. Yusuf OM. Streptococcus pyogenes upper respiratory infections and their effect on atopic conditions. Prim Care Respir J. Allergic rhinitis and its impact on asthma ARIA Kaliner M, McFadden F. Bronchial asthma. In: Samter S, editor. Immunological Diseases. Boston: Little Brown; Recent developments in united airways disease.
Allergy Asthma Immunol Res. Eccles C. Anatomy and physiology of the nose and control of nasal airflow. Philadelphia: Elsevier; Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg. Asthma, rhinitis, and skin test reactivity to aeroallergens in families of asthmatic subjects in Anqing, China. Eosinophils are a feature of upper and lower airway pathology in non-atopic asthma, irrespective of the presence of rhinitis.
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Allergol Int. Togias A. Mechanisms of nose-lung interaction. Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. Children with allergic and nonallergic rhinitis have a similar risk of asthma. IgE, mast cells, basophils, and eosinophils. Highly Influential.
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