Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Severe chronic rhinosinusitis treated with dupilumab, a real-life analysis of early effectiveness.

OBJECTIVE: The present study evaluated the safety and efficacy of dupilumab in severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps (CRSwNP). PATIENTS AND METHODS: A retrospective analysis was conducted on a cohort of adult patients affected by severe CRSwNP treated with dupilumab. Maxillofacial computed tomography, evaluation of blood eosinophils and serum IgE levels, measurement of nasal polyp score (NPS), smell identification test (SSIT-16), sinonasal outcome test-22 (SNOT-22) and asthma control test (ACT) were performed. Follow-up was conducted at 2 weeks, and at 1, 3, and 6 months. Adverse events and the efficacy of treatment were monitored. RESULTS: 23 patients were enrolled. After 15 days, scores of the SNOT-22, NPS and SSIT-16 significantly improved. These outcomes were also maintained after 1, 3, and 6 months (p < 0.001). At this latter follow-up time, SNOT-22 showed a change of -33.10 (p < 0.001), NPS -3.36 (p < 0.001) and SSIT-16 +5.60 (p < 0.001). In all, 26.1% of patients experienced early minor complications. CONCLUSIONS: In the present study, dupilumab was effective in the treatment of severe uncontrolled CRSwNP, demonstrating a quick significant improvement in both questionnaires and endoscopic evaluation. Only minor complications were observed.

Nasal cytology: Methodology with application to clinical practice and research.

Nasal cytology is an easy, cheap, non-invasive and point-of-care method to assess nasal inflammation and disease-specific cellular features. By means of nasal cytology, it is possible to distinguish between different inflammatory patterns that are typically associated with specific diseases (ie, allergic and non-allergic rhinitis). Its use is particularly relevant when other clinical information, such as signs, symptoms, time-course and allergic sensitizations, is not enough to recognize which of the different rhinitis phenotypes is involved; for example, it is only by means of nasal cytology that it is possible to distinguish, among the non-allergic rhinitis, those characterized by eosinophilic (NARES), mast cellular (NARMA), mixed eosinophilic-mast cellular (NARESMA) or neutrophilic (NARNE) inflammation. Despite its clinical usefulness, cheapness, non-invasiveness and easiness, nasal cytology is still underused and this is at least partially due to the fact that, as far as now, there is not a consensus or an official recommendation on its methodological issues. We here review the scientific literature about nasal cytology, giving recommendations on how to perform and interpret nasal cytology.

Evaluation of asthma control in the pharmacy: an Italian cross-sectional study.

SUMMARY: Background. In Western countries a large proportion of asthmatic patients remain uncontrolled, despite the availability of effective drugs. An involvement of pharmacies / pharmacists in asthma management has been suggested in guidelines, since this could provide a relevant support. Objective. The present cross-sectional study aimed at assessing the level of asthma control, by using ACT questionnaire, in the community pharmacies in the County of Verona, North East of Italy. Methods. A call for participation was sent by Verona Pharmacists' Association to all the pharmacies located in the Verona municipality. Patients with a medical prescription and an asthma exemption code were recruited in pharmacies. They were asked to fill the ACT questionnaire and to answer some additional questions on asthma treatment, smoke habits and comorbidities. Results. Thirty-seven community pharmacies recruited 239 patients. According to the ACT score, more than 50% of patients had a controlled asthma but 20% of them were totally uncontrolled and 12% were using oral steroid. Only 2.9% of patients had received an asthma action plan. Asthma was intermittent in 17.6% of patients, mild persistent in 13.8%, moderate persistent in 63.1% and severe in 5.4%. Discordance was observed between the self-perceived asthma control and objective parameters, when available. Of note, in the severe asthma group, most patients had an ACT > 20. Conclusion. This is the first Italian pharmacy-based study on asthma control. A better asthma control was recorded in this study in comparison with other trials, but about 50% of patients were insufficiently controlled. The community pharmacies can play a relevant role in the preliminary assessment of asthma control by using easy and not time consuming tools, such as ACT.

Italian Multicenter Cross-Sectional Study (AISAG) on light smoking and allergic diseases in adults.

Allergic rhinitis, allergic dermatitis, and food allergy are extremely common diseases and are frequently associated to each other and to asthma. Smoking is a potential risk factor for these conditions, but so far, results from individual studies have been conflicting. On the basis of these contradictory data in the literature we have carried out a multicenter cross-sectional study to evaluate the relationship between some allergic conditions and exposure or not to active light smoking. The study was carried out between May 2013 and November 2013 in 22 different Italian hospitals. Patients with respiratory and/or food allergy, and aged 18 years and over, visited at Allergy Outpatient Clinics, were invited to participate. A total of 1586 allergic patients (21.6% smokers) with a mean age of 39.2 years (standard deviation, SD = 15.1) were included. We demonstrated that the prevalence of tobacco smoking was higher in patients with food allergy and in asthmatic patients in stage III-IV. But no other statistical differences were found at univariate analysis. The sensitization patterns of non-smokers and smokers were similar. Furthermore, tobacco smoking was associated with higher risk of food allergy and lower risk of asthma. Moreover, tobacco smoking was an independent risk factor for persistent respect to intermittent rhinitis, and for asthma GINA stage III-IV with respect to stage I-II.

Multiple pulmonary nodules and unexplained fever: when the pulmonologist fails.

We describe herein a difficult case of persistent and refractory fever, associated with multiple lung nodules, progressive respiratory failure and general deterioration. Our patient was carefully investigated for the possible causes of his symptoms, using current and advanced diagnostic procedures, either serological or by imaging. The confirmatory diagnosis of anaplastic T-cell lymphoma, was obtained only after an invasive procedure (with severe pneumothorax), although it was too late. This suggests that also very rare diseases should be considered in the presence of unexplained signs/symptoms, and that in such cases, aggressive diagnostic procedures should be applied as early as possible.

Evaluation of house dust mite allergy in real life: patients' characteristics and satisfaction with treatment.

BACKGROUND: HDMs are a ubiquitous allergen source, with a very well defined biology, but their role in clinical settings and in everyday clinical practice is not well characterized. Aim of this cross-sectional, questionnaire-based study was to assess the clinical characteristics of HDM-related respiratory allergy in a large population of Italian patients. METHODS: A structured questionnaire was sent to allergists randomly chosen among those of the Italian Federation of Immunology, Allergy and Clinical Immunology (IFIACI). They were asked to fill it with the clinical data of 10-12 consecutive patients referred for respiratory allergy, positive to HDM skin prick test. The questionnaire assessed type and severity of allergy, demographics, yearly distribution of symptoms, treatment, and satisfaction with the therapy. RESULTS: 45 allergists collected data from 499 patients. Within the evaluated population, 42% had rhinitis only, 45% asthma + rhinitis and 13% asthma alone. Rhinitis was moderate/severe in 51% of patients. Asthma was intermittent in 36% of patients, mild in 37% and moderate in 27%. Conjunctivitis was the most frequent comorbidity (36%), followed by rhinosinusitis (16%), adenoid hypertrophy (6%) and polyposis (5%). Out of the population, 56.2% of patients were not at all or partially not satisfied of their treatment for rhinitis, whereas the percentage of dissatisfied patients was about 53% for asthma therapy. 34% patients (n = 170) were monosensitized to HDM. It is confirmed that patients have more symptoms during the fall-winter periods. CONCLUSION: Patients with HDM allergy have frequently moderate-severe rhinitis, and about 50% of them are not satisfied with their treatment.

Allergic and non-allergic rhinitis: relationship with nasal polyposis, asthma and family history.

Rhinitis and rhinosinusitis (with/without polyposis), either allergic or non-allergic, represent a major medical problem. Their associated comorbidities and relationship with family history have so far been poorly investigated. We assessed these aspects in a large population of patients suffering from rhinosinusal diseases. Clinical history, nasal cytology, allergy testing and direct nasal examination were performed in all patients referred for rhinitis/rhinosinusitis. Fibre optic nasal endoscopy, CT scan and nasal challenge were used for diagnosis, when indicated. A total of 455 patients (60.7% male, age range 4-84 years) were studied; 108 (23.7%) had allergic rhinitis, 128 (28.1%) rhinosinusitis with polyposis, 107 (23.5%) non-allergic rhinitis (negative skin test); 112 patients had associated allergic and non-allergic rhinitis, the majority with eosinophilia. There was a significant association between non-allergic rhinitis and family history of nasal polyposis (OR = 4.45; 95%CI = 1.70-11.61; p = 0.0019), whereas this association was no longer present when allergic rhinitis was also included. Asthma was equally frequent in non-allergic and allergic rhinitis, but more frequent in patients with polyposis. Aspirin sensitivity was more frequent in nasal polyposis, independent of the allergic (p = 0.03) or non-allergic (p = 0.01) nature of rhinitis. Nasal polyposis is significantly associated with asthma and positive family history of asthma, partially independent of the allergic aetiology of rhinitis.

Effects of pulmonary rehabilitation on lung function in chronic obstructive pulmonary disease: the FIRST study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) causes an impairment of respiratory function, well reflected by the progressive decrease in forced expiratory volume in 1 second (FEV1). The only interventions able to slow down the FEV1 decline are smoking cessation and drug treatment. Pulmonary rehabilitation (PR), is claimed to improve exercise tolerance, symptoms and quality of life, but its effects on lung function have been scantly investigated. AIM: The aim of this paper was to evaluate, by the study named "FEV1 as an Index of Rehabilitation Success over Time" (FIRST), the effects of PR on lung function in patients with COPD, under drug treatment with inhaled corticosteroids or long-acting ß2-agonists and/or tiotropium in various combinations, according to guidelines, during a 3-year period. DESIGN: Observational, prospective, with two parallel groups study. SETTING: PR setting in an urban hospital. POPULATION: Two hundred fifty-seven COPD patients, 190 (103 males, mean age 71.1 ± 7.1 years range 57-86 years) underwent PR and 67 (49 males, mean age 67.9 ± 7.9 years, range 58-79 years) were treated only with drugs. METHODS: Lung function was measured at baseline and at one-year intervals up to 3 years. The postbronchodilator FEV1 was used for statistical analysis. RESULTS: In the PR group, FEV1 increased from 1240 mL (57.3% of predicted value) to 1252.4 mL (60.8%) after 3 years, whereas in the controls the values were 1367 mL (55% of predicted) at baseline and 1150 mL (51%) after 3 years. This difference was statistically significant (P<0.001). CONCLUSION: In patients with COPD on standard pharmacotherapy, PR significantly affected the decline of FEV1 over time. CLINICAL REHABILITATION IMPACT: The ability to substantially stop the FEV1 decline seems exclusive of PR when added to drug treatment. This finding warrants confirmation from randomized trials.

IgG4: not only for allergists.

We describe herein a case of IgG4-related disease with the isolated clinical presentation of malabsorption due to pancreatic failure. Histology of an abdominal lymph node was critical for diagnosis. IgG4-related disease is increasingly recognized as an immunological disorder that can mimic various clinical entities.

Assessment of biofilm by nasal cytology in different forms of rhinitis and its functional correlations.

BACKGROUND: Recently, it has been reported that nasal cytology in light microscopy can identify biofilms, which appear as cyan-stained "Infectious Spots". We assessed by the same method and in the same population, the presence of biofilms in different nasal disorders, and estimated if a correlation with the functional grade of obstruction existed. METHODS: Subjects suffering from different nasal disorders, after a detailed clinical history and ENT examination, underwent nasal fibroendoscopy, skin prick test, rhinomanometry and nasal cytology. The presence of biofilm was linked to the type ofdisease and to the grade of obstruction. RESULTS: Among 1,410 subjects previously studied, the infectious spot was found in 107 patients (7.6%), and this percentage reached 55.4% in subjects with cytologic signs of infectious rhinitis (presence of bacteria/fungi). Biofilms were largely more frequent in patients with adenoid hypertrophy (57.4%), followed by nasal polyposis (24%), chronic rhinosinusitis (9.5%) and non-allergic rhinitis (7.6%). Nasal cytology was normal in the remaining patients, where no infectious spot was detectable. Statistical analysis showed that nasal resistances were significantly higher in presence of biofilms in patients with adenoid hypertrophy (p = 0.003), nasal polyposis (p < 0.001), chronic rhinosinusitis (p = 0.018) and septal deviation (p = 0.001). CONCLUSION: The results demonstrate that biofilm is present not only in infectious rhinitis, but also in inflammatory and/or immune-mediated diseases. The presence of biofilms significantly correlates with the degree of nasal obstruction as assessed by rhinomanometry.

The role of basophil activation test in special populations with mastocytosis and reactions to hymenoptera sting.

BACKGROUND: Systemic mastocytosis (SM) may be associated with hymenoptera allergy. In such cases, immunotherapy is a life-saving treatment, but a circumstantiated diagnosis is needed for its prescription. Patients with SM and previous reactions to stings, but with negative tests represent a diagnostic dilemma. The basophil activation test (BAT) may be helpful in refining the diagnosis. OBJECTIVE: We assessed the usefulness of BAT in subpopulations of mastocytosis patients, including those with negative tests for insect allergy. METHODS: Within a population of patients with mastocytosis and previous stings, we studied by BAT and augmented intradermal test (IDT) (10 µg/ml) two groups: (1) with reactions to stings and negative tests; (2) without reactions and negative tests. Basophil activation test was performed with different venoms, assessing at flow cytometry basophils' activation. RESULTS: Sixty-three patients had mastocytosis and 52 had reactions to previous hymenoptera stings. Of them, seven proved negative to diagnostic tests. In six of seven of those patients, BAT was negative with all venoms, and in one, basophils resulted activated also with the negative control. In six patients without previous reactions and negative tests, BAT was totally negative in five of six patients and weakly positive to Hornet in one. Finally, the IDT at 10 µg/ml venom produced nonspecific positive results in most cases. CONCLUSION: In patients with mastocytosis, the negative results of standard tests are reliable, because BAT and IDT at higher concentration do not add useful information.

Sensitization to horse allergens in Italy: a multicentre study in urban atopic subjects without occupational exposure.

BACKGROUND: Horses play a significant role in people's leisure time in Italy and other countries, but few data are available on IgE-mediated sensitization to horse allergens in patients without occupational exposure. We assessed, in a multicentric survey, the prevalence of horse sensitization in atopic subjects and its clinical characteristics. METHODS: Allergists from the whole Italian territory were required to collect the results of skin prick tests from at least 100 consecutive subjects. Those patients with a positive skin test to horse dander underwent a detailed interview concerning clinical history, pet ownership and possible exposure. RESULTS: Data from 3,235 outpatients were collected and 2,097 had at least 1 skin positivity. Among them, 113 (5.38%) were sensitized to horse dander (9 monosensitized). Thirty patients reported direct horse contact (4 owners and 26 for riding or occasional contact), 23 patients were sometimes in contact with horse owners and 60 subjects denied any direct or indirect exposure. Among 9 horse monosensitized patients, 6 had intermittent and mild rhinitis and 3 persistent moderate/severe rhinitis plus asthma. Three of them were horse owners or riders and the remaining had no contact with the animal. CONCLUSIONS: Our data evidence that the rate of sensitization to horse dander is not negligible and probably underestimated. In susceptible, not occupationally exposed individuals, horse contact, but also indirect or no apparent exposure, may induce sensitization. We recommend inclusion of horse allergen in the routine panel for the diagnosis of respiratory allergy.

How much specific is the association between hymenoptera venom allergy and mastocytosis?

BACKGROUND: The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs. METHODS: Patients with food- or drug-induced severe systemic reactions, including anaphylaxis, and increased serum tryptase were studied for the presence of mastocytosis, and compared with a population of patients with hymenoptera allergy. The aetiological role of foods or drugs was assessed according to current recommendations. Systemic reactions were graded in severity according to the procedure described by Mueller. Serum tryptase was considered increased if the level was >11.4 ng/ml. Subjects with increased tryptase had dermatological evaluation and Bone marrow(BM) aspirate-biopsy, which included histology/cytology, flow cytometry and detection of KIT mutations. RESULTS: A total of 137 subjects (57 male, mean age 42 years) were studied. Of them, 86 proved positive for drugs and 51 for foods. Overall, out of 137 patients, only nine (6.6%) had a basal tryptase >11.4 ng/ml, and only two (1.5%) were diagnosed with mastocytosis. This was clearly different from patients with hymenoptera allergy, where 13.9% had elevated tryptase and 11.1% had a clonal mast cell disorder. CONCLUSION: The association of clonal mast cell disorders with hymenoptera allergy seems to be more specific than that with food- or drug-induced systemic reactions.

Melkersson-Rosenthal syndrome associated with parvovirus B19 viraemia and haemophagocytic lymphohistiocytosis.

We describe a 23-year-old patient who presented acutely with haemophagocytic lymphohistiocytosis (HL) and Melkersson-Rosenthal syndrome (MRS). MRS and HL are two unusual and complex clinical patterns that may present acutely and to our knowledge, an association between them has never been reported. The clinical investigations in this patient led to identification of parvovirus B19 (PB19) viraemia by PCR. Parvovirus infection has been reported as a cause of virus-associated HL, but the presence of PB19 has never been sought or reported as a possible trigger for MRS. This observation suggests a possible association between PB19 and HL, and opens the possibility of its association also with acute-onset MRS. Further investigations for the presence of PB19 in cases of MRS are warranted.

Inmunoterapia específica para enfermedades alérgicas respiratorias: estado de la cuestión de acuerdo a los metanálisis actuales / Specific inmunotherapy for respiratory allergy: state of the art according to current meta-analyses

Objetivos: evaluar la eficacia de la inmunoterapia alergeno especifica (IT)en el tratamiento del asma y la rinitis alérgica de niños y adultos, mediante el examen de diferentes metanálisis (MTA) realizados hasta la actualidad.

Effect of statins on fibroblasts from human nasal polyps and turbinates.

BACKGROUND: Statins are serum cholesterol-lowering agents used for the prevention and treatment of atherosclerotic vascular disease. There is, however, growing evidence that statins have immunomodulatory and anti-inflammatory activities and may prove invaluable in the treatment of immunological and inflammatory disorders. OBJECTIVE: On these basis we evaluated the effect of statins on the proliferation of fibroblasts derived from human nasal polyps and turbinates and determined their ability to modulate airway remodelling. METHODS: Fluvastatin (0.01-0.1-1 microM), Atorvastatin (0.1-1-10 microM) and Simvastatin (0.1-1-10 microM) were tested on cultured fibroblasts derived from human nasal polyps and turbinates stimulated or not with Fibroblast Growth Factor beta (10 ng/ml). All cultures were treated with 3H-Thymidine (1 microCi/ml) to test cell proliferation. RESULTS: Our results show that proliferation of turbinate-derived fibroblasts is significantly inhibited by the three statins. Fluvastatin is already effective at the lowest dose (0.01 microM), whereas Atorvastatin and Simvastatin act at the plasmatic peak concentration (1 microM). No significant effect was found on fibroblasts derived from nasal polyps, except for Simvastatin which was effective after 144 hours of stimulation. CONCLUSIONS: These drugs show a remarkable antiprolhferative effect and their different outcome depending on the different kind of fibroblasts in vitro is prompting news in the studies about statin use for the treatment of chronic inflammatory diseases.

Efectos preventivos de la inmunoterapia sublingual en niños: un estudio abierto, aleatorizado y controlado / Preventive effects of sublingual immunotherapy in childhood: an open randomized controlled study

Objetivos. Evaluar los efectos clínicos y preventivos de la inmunoterapia sublingual (SLIT) con respecto a la aparición de asma persistente, nuevas sensibilizaciones, síntomas clínicos e hiperreactividad bronquial (HRB). Los objetivos secundarios fueron: evaluar la magnitud del efecto clínico y el efecto sobre la HRB; ver la seguridad y adhesión a la SLIT. Material y métodos: Participaron 216 niños, de ambos sexos, entre 5 y 17 años, pacientes del Hospital Cuasso al Monte, Varese, Italia, con rinitis alérgica de al menos 2 años de evolución, con o sin síntomas de asma intermitente, y con diagnóstico de etiología alérgica confirmado para ácaros, gramíneas, árboles y malezas. Se excluyeron pacientes con asma persistente o VEF1 <80%, uso previo de inmunoterapia, anormalidades anatómicas de las vías aéreas superiores, enfermedades sistémicas crónicas (malignas o autoinmunes) y sensibilizaciones a epitelios y hongos anemófilos. Para los diagnósticos de rinitis y asma se emplearon las guías actuales (ARIA, GINA). Se realizaron prick test con panel estándar de alérgenos relevantes (ALK Abelló), histamina 1% y control negativo al principio y al final del estudio. Las pruebas de función pulmonar consistieron en espirometría computarizada con cabina pletismográfica y prueba de provocación no específica con metacolina con dosis progresivas desde 30 a 1.290 µg, durante el período de máxima exposición alérgenica según sensibilidad de cada paciente, al inicio y al final del estudio. A los pacientes con prueba negativa (descenso del VEFI <20%) se los consederaba con diagnóstico de rinitis exclusivamente. El estudi tuvo un período basal de 1 año de observación y luego una fase de aleatorización de 3 años de tratamiento abierto con dos ramas. Un grupo de pacientes utilizó drogas exclusivamente, y otro grupo drogas más SLIT (con una distribución 1/2).