Chronic rhinosinusitis and nasal polyposis in cystic fibrosis: update on diagnosis and treatment

Review Article Chronic rhinosinusitis and nasal polyposis in cystic fibrosis: update on diagnosis and treatment * Suzie Hyeona Kang Paulo de Tarso Roth Dalcin Otavio Bejzman Piltcher Raphaella de Oliveira Migliavacca 1Doctoral Student. Graduate Program in Pulmonology, Federal University of Rio Grande do Sul School of Medicine, Porto Alegre, Brazil 2Associate Professor. Graduate Program in Pulmonology, Federal University of Rio Grande do Sul School of Medicine, Porto Alegre, Brazil 3Adjunct Professor. Department of Ophthalmology and Otolaryngology, Federal University of Rio Grande do Sul School of Medicine, Porto Alegre, Brazil 4Otolaryngologist. Department of Otolaryngology and Head & Neck Surgery, Federal University of Rio Grande do Sul School of Medicine Hospital de Clínicas, Porto Alegre, Brazil ABSTRACT Although cystic fibrosis (CF) is an irreversible genetic disease, advances in treatment have increased the life expectancy of CF patients. Upper airway involvement, which is mainly due to pathological changes in the paranasal sinuses, is prevalent in CF patients, although many are only mildly symptomatic (with few symptoms). The objective of this literature review was to discuss the pathophysiology and current therapeutic management of chronic rhinosinusitis (CRS) in CF patients. The review was based on current evidence, which was classified in accordance with the Oxford Centre for Evidence-Based Medicine criteria. When symptomatic, CRS with nasal polyps can affect quality of life and can lead to pulmonary exacerbations, given that the paranasal sinuses can be colonized with pathogenic bacteria, especially Pseudomonas aeruginosa. Infection with P. aeruginosa plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Although clinical treatment of the upper airways is recommended as initial management, this recommendation is often extrapolated from studies of CRS in the general population. When sinonasal disease is refractory to noninvasive therapy, surgery is indicated. Further studies are needed in order to gain a better understanding of upper airway involvement and improve the management of CRS in CF patients, with the objective of preserving lung function and avoiding unnecessary invasive procedures. Key words: Nose diseases; Cystic fibrosis; Nasal polyps; Paranasal sinuses; Sinusitis Introduction Cystic fibrosis (CF) is an autosomal recessive disease that is irreversible. It has been mapped on the long arm of chromosome 7 (7q31), which encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Approximately 1,000 CF-causing mutations have been identified, the most common being ΔF508.( 1 ) In general, CF presents as multisystem impairment, characterized by progressive lung disease, exocrine pancreatic insufficiency, liver disease, intestinal motility disorder, male infertility, and high concentrations of sweat electrolytes as a result of mucus hyperviscosity.( 2 ) It is well established that CF patients have upper airway involvement, and many develop chronic rhinosinusitis (CRS), which has a negative effect on their quality of life. Advances in treatment have increased the life expectancy of CF patients in recent years.( 3 ) This increase in life expectancy has increased the focus on the management of comorbidities, including sinonasal disease. The objective of the present review was to discuss the pathophysiology, symptoms, diagnosis, and therapeutic management of sinonasal disease in CF patients, as well as the influence of CRS on lung disease in such patients. Methods We searched the MEDLINE (PubMed), SciELO, and Cochrane Library databases using the search terms and Boolean operators (cystic fibrosis [Title]) AND (sinusites [Title/Abstract] OR paranasal sinuses [Title/Abstract] OR upper airways [Title/Abstract]) in order to identify titles and abstracts of original and review articles published between 1960 and 2013. The search was limited to articles in English, Spanish, or Portuguese. We selected the most recent and relevant articles in order to provide an update on the treatment of sinonasal disease in CF patients. Criteria for the diagnosis of CRS and nasal polyposis According to the European Position Paper on Rhinosinusitis and Nasal Polyps 2012,( 4 ) rhinosinusitis in adults is defined as inflammation of the nose and paranasal sinuses with two or more of the following symptoms: nasal congestion anterior or posterior nasal drip facial pain or pressure reduction or loss of smell These symptoms can be accompanied by endoscopic signs (of nasal polyps, mucopurulent discharge primarily from the middle meatus, edema/mucosal obstruction primarily in the middle meatus, or any combination of the three), radiographic changes in the paranasal sinuses, or both. On the basis of its duration, the disease can be classified as acute/intermittent (< 12 weeks with complete resolution of symptoms) or chronic/persistent (≥ 12 weeks without complete resolution of symptoms). Nasal polyposis is considered to be a subgroup of CRS.( 4 ) In patients with CF, the finding of extensive radiographic changes in the absence of symptoms or endoscopic signs is common, its true clinical significance being unclear.( 5 ) Epidemiology Although CF has a varied phenotypic presentation, pulmonary and sinonasal involvement occurs in 90-100% of CF patients.( 6 ) Approximately 80% of patients with CF have nasal obstruction, 25% have anosmia, and more than 50% complain of rhinorrhea and headache.( 7 ) The prevalence of nasal polyposis in patients with CF appears to depend on age, increasing during adolescence and ranging from 6% to 48%.( 8 ) Pathogenesis of sinonasal disease in CF patients Although ciliary structure and beat frequency are normal in CF patients, many factors appear to contribute to impaired mucociliary clearance in such patients. First, changes in the viscoelastic properties of mucus, which are secondary to abnormal chloride conductance, appear to have a crucial role in the development of sinonasal disease. Colonization with Pseudomonas aeruginosa, which has a high affinity for the respiratory mucosa, also appears to contribute to impaired clearance. The presence of bacteria releases many substances, including homolysine and phenazine derivatives. They reduce ciliary beat frequency, and chronic inflammation causes goblet cell hyperplasia, squamous metaplasia, and hair cell loss. Macroscopically, these factors lead to sinus ostial obstruction, resulting in infected mucus stasis, local inflammation, and impaired gas exchange. Increased PaCO2 causes mucosal edema, decreased ciliary function, and, consequently, bacterial colonization.( 1 ) It has been suggested that there is a relationship between the genotype-phenotype correlation and CRS. A high risk of nasal polyposis has been found in patients homozygous for (...truncated)