Basic assessment of chronic cough in primary care and referral pathways of patients to different specialists: plain language summary of publication.

People with chronic cough (a cough lasting more than 8 weeks) are often referred to different specialists and undergo numerous diagnostic tests, but clear guidance is lacking. This work summarizes a consensus (an agreement) among medical specialists who are involved in managing people with chronic cough: primary care physicians (family doctors), pulmonologists (doctors who specialize in lung conditions), allergists (medical professionals specializing in allergies) and ear, nose and throat (ENT) specialists. They discussed how to perform a basic assessment of people with chronic cough in primary care (day-to-day healthcare given by a general practitioner or family doctor) and how to refer them to different specialists based on clinical findings or test results.

Long-Term Clinical Outcomes in Patients with Chronic Rhinosinusitis with Nasal Polyps Associated with Expanded Types of Endoscopic Sinus Surgery.

(1) Background: Surgical criteria for chronic rhinosinusitis with nasal polyps (CRSwNP) remain unresolved. This study addresses these discrepancies by comparing the clinical outcomes of expanded-functional endoscopic sinus surgeries (E-FESS) with more-limited FESS (L-FESS). (2) Methods: A database was analyzed retrospectively to compare surgical outcomes in CRSwNP patients who underwent E-FESS versus those subjected to L-FESS. Quality of life, endoscopic and radiological outcomes were compared at the baseline and two years after surgery. The clinical status of the responder was defined when a minimal clinically important difference of 12 points in SNOT-22 change was achieved. (3) Results: A total of 274 patients met the inclusion criteria and were analyzed; 111 underwent E-FESS and 163 were subjected to L-FESS. Both groups exhibited significant clinical improvements, although a greater magnitude of change in SNOT-22 (14.8 ± 4.8, p = 0.002) was shown after E-FESS. Higher significant improvements for endoscopic and radiological scores and lower surgical revision rates were also noted in the E-FESS group. (4) Conclusions: E-FESS provides better clinical outcomes and reduced revision surgery rates when compared to L-FESS in CRSwNP patients two years after surgery, irrespective of any comorbidity. Further randomized prospective studies are needed to comprehensively contrast these results.

Basic assessment of chronic cough in primary care and referral pathways of patients to different specialists.

BACKGROUND: Chronic cough (CC; cough that lasts 8 weeks or longer) poses major effective assessment challenges. Assessment of CC may vary considerably among medical specialists. OBJECTIVES: The aim was to evaluate similarities and consistency of responses across different specialists when performing a basic assessment of CC patients in primary care, and referring patients based on clinical findings or test results. METHODS: A modified Delphi approach was used. A survey with 74 statements on initial assessment of CC and referral pathways was addressed to a panel of different specialists, who voted the statements in two rounds. RESULTS: Seventy-seven physicians [18 primary care physicians (PCPs), 24 pulmonologists, 22 allergists, and 13 ear, nose, and throat specialists] from the National Healthcare System of Spain answered the questionnaire. After two rounds, the panel reached a consensus on 63 out of the 74 proposed items (85.1%). Consensus was not reached among the panelists of at least one specialty on 15 out of these 63 agreed items. The panel agreed on those clinical aspects that should be evaluated by PCPs in all patients with CC including the impact of CC on quality of life. Agreement was reached on initial actions to be taken in primary care, including substitution of drugs that may induce cough, performing a chest X-ray, introduction of anti-reflux measures, initiation of empirical anti-reflux pharmacological therapy in some cases, and performing a spirometry with bronchodilator test and hemogram if an etiological diagnosis was not reached. The panelists agreed on a list of diseases that PCPs should assess before referring CC patients. Algorithms were developed for initial assessment and targeted referral of patients with CC from primary care. CONCLUSION: This study provides the perspective of different medical specialists on how to perform a basic assessment of CC patients in primary care and how and when to refer patients to other specialists.

Consensus on the management of united airways disease with type 2 inflammation: a multidisciplinary Delphi study.

BACKGROUND: Scientific evidence on patients with multimorbid type 2 asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) from a united airways disease (UAD) perspective remains scarce, despite the frequent coexistence of these entities. We aimed to generate expert consensus-based recommendations for the management of UAD patients. METHODS: Using a two-round Delphi method, Spanish expert allergists, pulmonologists and otolaryngologists expressed their agreement on 32 statements (52 items) on a 9-point Likert scale, classified as appropriate (median 7-9), uncertain (4-6) or inappropriate (1-3). Consensus was considered when at least two-thirds of the panel scored within the range containing the median. RESULTS: A panel of 30 experts reached consensus on the appropriateness of 43 out of the 52 (82.7%) items. The usefulness of certain biomarkers (tissue and peripheral blood eosinophil count, serum total IgE, and fraction of exhaled nitric oxide [FeNO]) in the identification and follow-up of type 2 inflammation, and assessment of the response to biologics, were agreed. Some of these biomarkers were also associated with disease severity and/or recurrence after endoscopic sinus surgery (ESS). Consensus was achieved on treatment strategies related to the prescription of anti-IL-4/IL-13 or anti-IgE agents, concomitant treatment with systemic corticosteroids, and combining or switching to biologics with a different mechanism of action, considering a number of UAD clinical scenarios. CONCLUSION: We provide expert-based recommendations to assist in clinical decision-making for the management of patients with multimorbid type 2 asthma and CRSwNP. Specific clinical trials and real-world studies focusing on the single-entity UAD are required to address controversial items.

Analysis of Prevalence and Predictive Factors of Long-Lasting Olfactory and Gustatory Dysfunction in COVID-19 Patients.

BACKGROUND: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. METHODS: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT. RESULTS: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS (r = -0.36, p = 0.0027). CONCLUSION: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests.

Loss of Smell and Taste Can Accurately Predict COVID-19 Infection: A Machine-Learning Approach.

The COVID-19 outbreak has spread extensively around the world. Loss of smell and taste have emerged as main predictors for COVID-19. The objective of our study is to develop a comprehensive machine learning (ML) modelling framework to assess the predictive value of smell and taste disorders, along with other symptoms, in COVID-19 infection. A multicenter case-control study was performed, in which suspected cases for COVID-19, who were tested by real-time reverse-transcription polymerase chain reaction (RT-PCR), informed about the presence and severity of their symptoms using visual analog scales (VAS). ML algorithms were applied to the collected data to predict a COVID-19 diagnosis using a 50-fold cross-validation scheme by randomly splitting the patients in training (75%) and testing datasets (25%). A total of 777 patients were included. Loss of smell and taste were found to be the symptoms with higher odds ratios of 6.21 and 2.42 for COVID-19 positivity. The ML algorithms applied reached an average accuracy of 80%, a sensitivity of 82%, and a specificity of 78% when using VAS to predict a COVID-19 diagnosis. This study concludes that smell and taste disorders are accurate predictors, with ML algorithms constituting helpful tools for COVID-19 diagnostic prediction.

Validation of the DECA criteria for allergic conjunctivitis severity and control.

BACKGROUND: Allergic conjunctivitis (AC) is usually associated to allergic rhinitis (AR), but the severity and control of ocular symptoms should be assessed independently to improve diagnosis and treatment. The criteria from the Spanish consensus document on allergic conjunctivitis (DECA) aimed to be used as a patient-reported instrument for AC management. Here we validate these criteria for classifying AC severity and defining its control following COSMIN guidelines recommendations. METHODS: Patients with moderate or severe AR [reflective total nasal symptom score (rTNSS) score ≥ 8] and concomitant AC were recruited from hospitals in Spain. Patients were classified according to the severity of ocular symptoms as mild, moderate, or severe, and classified with respect to control as controlled and non-controlled, using the DECA criteria. To validate these criteria, comparisons with the validated modified allergic rhinitis and its impact on asthma (mARIA), reflective total ocular symptom score (rTOSS), rhinitis control assessment test (RCAT), ESPRINT-15 questionnaires, a conjunctival hyperemia scale and a visual analogue scale (VAS) for ocular symptoms were performed. RESULTS: A total of 128 patients participated in the validation. Mean age was 34.4 ± 12.1 years; 72.7% were women. The DECA criteria showed a good discriminant validity, reflecting a high capacity to differentiate between mild, moderate, and severe patients, and controlled from uncontrolled patients. A strong association between AC and AR was reflected in the comparison between the DECA and the mARIA criteria (p < 0.0001). The DECA criteria for severity and control presented satisfactory properties for longitudinal validity and responsiveness. CONCLUSIONS: Validation of the DECA criteria for severity and control of AC suggested that it can be useful in the evaluation of eye symptoms and follow-up of therapies.

Rhinitis Phenotypes.

Rhinitis is an umbrella term of a group of upper airway diseases with nasal symptoms and signs with different etiologies and various clinical features or traits. It can be classified into different "phenotypes," based on these observable traits. A proper differential diagnosis is necessary to adequately manage the disease. The objective of this review is to clarify the concept of rhinitis phenotypes while analyzing the clinical features and/or traits of each in order to determine a proper differential diagnosis and appropriate treatment.

Allergic rhinitis causes loss of smell in children: The OLFAPEDRIAL study.

BACKGROUND: The objective of the OLFAPEDRIAL study was to assess the olfactory dysfunction in allergic paediatric population, which has been scarcely studied. METHODS: Observational, cross-sectional and multicentre study evaluated the sense of smell in untreated allergic rhinitis (AR) paediatric patients aged 6-12 years. RESULTS: Forty-four per cent (551 of 1260) of children with AR reported smell dysfunction, with both loss of smell frequency (52.1%, p < 0.001) and intensity (0.75 ± 0.84, p < 0.0001) being more frequent in patients with persistent than intermittent AR (38.0% and 0.51 ± 0.73, respectively). In addition, both loss of smell frequency and intensity increased according to disease severity (m-ARIA classification) but always being significantly higher in persistent (p < 0.0001) than in intermittent AR. CONCLUSIONS: Children with allergic rhinitis present a mild-moderate loss of smell frequency and intensity which is clearly related to the disease duration and severity. The loss of smell can be considered, as in adults, a clinical marker of disease severity.

Analysis of comorbidities and therapeutic approach for allergic rhinitis in a pediatric population in Spain.

BACKGROUND: Allergic rhinitis (AR) is the most common chronic disease in children. The main objective of this study was to analyze the comorbidities and therapeutic approaches for AR in a Spanish pediatric population. METHODS: Children aged 6 to 12 years with AR were included in an observational, cross-sectional, multicenter study. RESULTS: 1,275 children were recruited from 271 centers. AR was intermittent in 59.5% of cases, persistent in 40.5%, seasonal in 60.7%, and perennial in 39.3% of patients. The most frequent comorbidities were conjunctivitis (53.6%), asthma (49.5%), atopic dermatitis (40%), rhinosinusitis(26.1%), otitis media (23.8%), and adenoid hypertrophy (17.3%). Overall, patients with persistent, moderate or severe, AR were more likely to present comobidities, except for food allergy and urticaria. The most common drugs used for treatment of AR were oral antihistamines(76%), nasal corticosteroids(49%) and a combination of both (45%). Antihistamines and nasal corticosteroids were used on demand (<18 days) in 38 and 41% of patients, respectively; for 18-30 days in 22 and 27%; for 1-3 months in 31 and 29%; and for more than 3 months in 8 and 3%, respectively. Eye drops were used in 32% and specific immunotherapy in 21% of patients. CONCLUSION: Comorbidities are frequent in children with AR, supporting the notion of allergy as a systemic disease. Severity and duration of AR were significantly associated with presence of most of comorbidities. The most common drugs used for AR treatment were oral antihistamines, followed by nasal corticosteroids and a combination of both used on demand.

Bilastine for the treatment of urticaria.

INTRODUCTION: Urticaria is a highly prevalent disease among people. First-choice treatment continues to be centred on the second-generation H1 antihistamines, including a wide group of drugs with a better therapeutic index (or risk:benefit ratio) than the classic ones, even in the high, off-label dosage occasionally required in chronic urticaria. Bilastine is a newly registered H1-antihistamine for treatment of allergic rhinoconjunctivitis and urticaria. With established antihistaminic and antiallergic properties, it is widely reviewed in the medical literature; however, to our knowledge, a specific review of bilastine's role in the treatment of urticaria was lacking. AREAS COVERED: This article reviews the medical literature on the effectiveness and safety of bilastine in urticarial syndromes, either spontaneous or inducible, by means of a Medline search from 1990 to present, completed with some nonpublished data provided by the manufacturer. EXPERT OPINION: Once-daily treatment with bilastine 20 mg is effective in managing symptoms and improving patient's quality of life in chronic urticaria, with at least comparable efficacy to levocetirizine. As far as studies in healthy volunteers, clinical assays, and recent clinical experience can establish, bilastine's safety profile is adequate, appearing to be entirely free from cardiovascular effects, and not impairing psychomotor performance or actual driving, even at twice the therapeutic dose.

The impact of allergic rhinitis on symptoms, and quality of life using the new criterion of ARIA severity classification.

INTRODUCTION: Allergic rhinitis (AR) is a common disease with major socieconomic burden and a significant impact on quality of life. OBJECTIVE: The objective of the study was to assess the impact of AR severity, using the modified ARIA (m-ARIA) severity criterion in order to discriminate among moderate and severe AR, in symptoms and quality of life assessed with the questionnaire ESPRINT-15. METHODS: The specific quality of life questionnaire (ESPRINT-15) was applied in over thousand untreated RA patients. Severity was evaluated by the m-ARIA classification, which categorizes AR as mild, moderate, and severe. Nasal symptoms were evaluated by using categorized (none, low, middle, and high) Total Four Symptom Score (T4SS). RESULTS: Using the m-ARIA severity classification, significant differences in quality of life, both global score and specific domains, and categorized T4SS were found among the AR severity groups. CONCLUSION: Modified ARIA severity classification in mild, moderate, and severe allergic rhinitis clearly discriminates the impact of AR in all domains of quality of life and categorized symptom`s score.

Validation of ARIA (Allergic Rhinitis and its Impact on Asthma) classification in a pediatric population: the PEDRIAL study.

Allergic rhinitis (AR) is the commonest chronic disease in children. Allergic Rhinitis and its Impact on Asthma (ARIA) classification based on symptom duration (intermittent vs. persistent) and severity (mild vs. moderate/severe) has not been yet validated in children. Thus our objective was to validate ARIA classification in children, after determining the severity and duration of AR in a pediatric population, using ARIA definitions. Children aged 6-12 with a diagnosis of AR were included in an observational, cross-sectional, multicenter study. Patients were classified according to ARIA guidelines. AR symptoms were assessed using the Total Four Symptoms Score (T4SS). Severity was also evaluated by the patient using a visual analogue scale (VAS). Comparisons were made by means of a statistical analysis. One thousand two hundred and seventy-five children from 271 centers were included. Among them, 59.5% had intermittent and 40.5% persistent AR, while 60.7% seasonal and 39.3% perennial according to dated classification, with significant differences existing between one classification and another; 89.7% had moderate/severe rhinitis. Significantly higher T4SS and VAS scores were obtained in moderate/severe compared to mild AR. In our experience, the current ARIA classification can be considered a valid tool also in children from 6- to 12-yr old.

Validation of ARIA duration and severity classifications in Spanish allergic rhinitis patients - The ADRIAL cohort study.

INTRODUCTION: Allergic rhinitis (AR) is an increasingly prevalent worldwide disease, which has an important impact on quality of life and generates high social and health care costs. The ARIA classification, that considers both the duration and severity of AR, seems more appropriate than previous classifications of AR, but few studies exist on the validation of the severity criteria proposed by the ARIA classification. OBJECTIVES: To assess the ARIA duration and severity classification of AR in a large sample population of patients, by investigating whether different degrees of severity correlate with differences in symptom score, quality of life or the patient's self evaluation of impairment. This study also assesses the relationship between AR severity and co morbidities. MATERIAL AND METHODS: An observational, cross-sectional, multicentre study conducted in Spain. AR was classified based on the ARIA criteria, and compared to the classical classification based on allergen exposure. Rhinitis was evaluated by the Total 4-Symptom Score (T4SS) scale, quality of life was measured using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and disease severity through a Visual Analogue Scale (VAS, 0-100 mm). Comorbidities were evaluated based both on the duration and severity of the symptoms of rhinitis. RESULTS: AR patients, (n = 3,529; mean age 37.5 +/= 13.4 years; 52.3% women) were included in the study. AR patients were classified as intermittent (51.5%) and persistent (48.5%) based on the ARIA classification, and as seasonal (61.2%), perennial (35.1%), and occupational (3.7%) based on the allergen exposure classification. Significantly higher T4SS, RQLQ and VAS scores were obtained in moderate/severe compared to mild AR. The incidence of asthma was significantly higher in patients with persistent and moderate/severe AR compared to intermittent and mild AR. Asthma was the only co morbidity to reach statistical significance. CONCLUSION: ARIA classification of severity reflects two different statuses of AR in terms of symptoms and quality of life. Asthma was the only concomitant pathology in which incidence was related to ARIA categories in terms of duration or severity.

Safety of rupatadine administered over a period of 1 year in the treatment of persistent allergic rhinitis: a multicentre, open-label study in Spain.

BACKGROUND: Rupatadine (Rupafin), a novel antihistamine approved recently in Europe for the treatment of allergic rhinitis (AR) and chronic idiopathic urticaria in patients aged>or=12 years, has been shown to be highly efficacious, and as safe and well tolerated as other commonly employed antihistamines in the treatment of allergic disease. There are, however, few data on the long-term safety of these antihistamines derived in accordance with the clinical safety recommendations of the European Agency for the Evaluation of Medicinal Products (EMEA) and the International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline. OBJECTIVE: To assess the safety and tolerability of treatment with rupatadine 10 mg/day for 12 months in subjects with persistent AR (PER). METHODS: A multicentre, open-label, phase IV study in patients recruited from 33 centres in Spain, from September 2002 to November 2005. The study enrolled 324 male and female patients (aged 12-70 years) with a medical history of PER for at least 12 months and a documented positive skin-prick test to an appropriate allergen. On 4 of the 7 days prior to start of treatment, the patients were required to have a minimum total nasal symptom score (TNSS [for sneezing, rhinorrhoea, nasal obstruction/congestion and nasal itching]) of >or=5. Of the 324 eligible patients starting treatment, 120 needed to be treated for more than 6 months and were followed up until the end of 12 months. All patients received rupatadine 10 mg/day and were allowed to continue their normal concomitant medication for all conditions, other than rhinitis, for up to 6 or 12 months. Safety was assessed by means of adverse events (AEs) reported by patients or detected by investigators, scheduled centralized ECG with special attention to Bazzet corrected QT interval (QTcB) and standard laboratory investigations. RESULTS: Assessment of treatment compliance rates indicated 90% and 83% of patients to be compliant during the 1-6 months and 1-12 months treatment periods, respectively, with compliance rates>80% being associated with the majority of the study population reporting at least one AE. Overall, 74.1% and 65.8% of the patients reported at least one AE during the 1-6 months and 1-12 months treatment periods, respectively, compared with 20.4% and 10.8% of patients reporting at least one treatment-related AE during these periods. Disorders of the nervous system and respiratory thoracic and mediastinal system, in particular headache, somnolence and catarrh, were the three most common AEs reported by >5% of the patients during both treatment periods. Detailed ECG assessments demonstrated no clinically relevant abnormal ECG findings, nor any QTcB increases >60 msec or QTcB values>470 msec for any patient at any time during treatment. Serious AEs were reported in seven patients, of whom six were considered as unlikely to be related to rupatadine treatment, whereas one involving increased blood enzyme levels was considered as possibly related to rupatadine treatment. CONCLUSION: This study confirmed the good long-term safety and tolerability of rupatadine at the therapeutic dose of 10 mg/day in patients with PER.

Development and validation of a new Spanish instrument to measure health-related quality of life in patients with allergic rhinitis: the ESPRINT questionnaire.

OBJECTIVES: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations. METHODS: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.