RESUMO
The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.
Assuntos
Hipersensibilidade , Medicina de Precisão , Alérgenos , Dessensibilização Imunológica , Genômica , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapiaRESUMO
BACKGROUND: Introduction and gradual incremental escalation of a low dose of baked egg may accelerate the resolution of severe hen's egg (HE) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked egg oral immunotherapy (OIT) in children with HE allergy after a low-dose baked egg oral food challenge (OFC). METHODS: In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 71 children with HE allergy and high egg-white (EW) and ovomucoid specific IgE levels, who underwent a total of 164 OFC (71 baked egg, then 93 unbaked egg). Mean age at first low-dose baked egg OFC was 6 years. Median EW specific IgE was 14.0 kUA/L, and median ovomucoid specific IgE was 11.7 kUA/L. RESULTS: Most children were treated with baked egg OIT. Our study shows that 78.9% of the children did not react to first low-dose baked egg OFC (702 mg of HE protein). 8.7% of children discontinued OIT at home. Finally, desensitization to unbaked HE was achieved in 47 children (66.2% of children allergic to HE). Children with lower EW specific IgE levels had a significantly higher probability of becoming desensitized to HE. We did not report any anaphylactic reactions to baked egg OIT. CONCLUSION: Most children with HE allergy and high egg-white (EW) and ovomucoïd specific IgE levels tolerate the introduction of baked egg. Baked egg OIT is safe, and anaphylaxis to baked egg OIT has not been observed.
Assuntos
Hipersensibilidade a Ovo , Administração Oral , Alérgenos , Animais , Galinhas , Criança , Dessensibilização Imunológica , Hipersensibilidade a Ovo/terapia , Ovos , Feminino , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Mepolizumab was available in France as part of an early access programme for patients with severe eosinophilic asthma (nominative autorisation temporaire d'utilisation [temporary use authorisation] (nATU)) before its commercialisation. This study aimed to characterise patients who received mepolizumab in the nATU. METHODS: This retrospective, observational study analysed data from the hospital medical records of patients up to 24â months after treatment initiation. Study objectives were to describe patient baseline characteristics, the evolution of disease severity and treatment modifications during follow-up; safety was also investigated. FINDINGS: Overall, 146 patients who received ≥1 dose of mepolizumab were included. At inclusion, patients had a mean age of 58.2â years with a mean severe asthma duration of 13.4â years, and 37.0% had respiratory allergies. Patients experienced, on average, 5.8 exacerbations per patient per year at baseline, 0.6 and 0.5 of which required hospitalisation and emergency department visits, respectively. These values improved to 0.6, 0.1 and 0.1 exacerbations per patient per year, respectively, at 24â months of follow-up. Most patients (92.8%) were using oral corticosteroids at baseline, compared with 34.7% by 24â months of follow-up. Moreover, mean blood eosinophil counts improved from 722â cells·µL-1 at baseline to 92â cells·µL-1 at 24â months of follow-up; lung function and asthma control followed a similar trend. INTERPRETATION: Results confirm findings from clinical trials, demonstrating that mepolizumab is associated with important improvements in several clinically meaningful outcomes and has a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial.
Assuntos
Antiasmáticos , Anticorpos Monoclonais Humanizados , Asma , Corticosteroides/uso terapêutico , Antiasmáticos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Asma/tratamento farmacológico , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Dupilumab is a monoclonal anti-IL-4Rα antibody developed for the treatment of severe asthma (SA). An early access programme for dupilumab was opened in France in SA patients experiencing unacceptable steroids side-effects and/or life-threatening exacerbations. OBJECTIVE: To assess changes in asthma control between baseline and 12 months of treatment. METHODS: Multi-centre (n = 13) retrospective real-life cohort study. This study is registered on ClinicalTrials.gov (NCT04022447). RESULTS: Overall, 64 patients with SA (median age 51, interquartile range [44-61]; 53% females) received dupilumab as add-on therapy to maximal standard of care; and 76% were on oral daily steroids at baseline. After 12 months, median asthma control test score improved from 14 [7-16] to 22 [17-24] (P < .001); median forced expiratory volume in 1 seconds increased from 58% [47-75] to 68% [58-88] (P = .001); and daily prednisone dose was reduced from 20 [10-30] to 5 [0-7] mg/d (P < .001). Annual exacerbations decreased from 4 [2-7] to 1 [0-2] (P < .001). Hypereosinophilia ≥1500/mm3 was observed at least once during follow-up in 16 patients (25%), persisting after 6 months in 8 (14%) of them. Increase in blood eosinophil count did not modify the clinical response during the study period. Injection-site reaction was the most common side effect (14%). Three deaths were observed, none related to treatment by investigators. CONCLUSION & CLINICAL RELEVANCE: In this first real-life cohort study of predominantly steroid-dependent SA, dupilumab significantly improved asthma control and lung function and reduced oral steroids use and exacerbations rate. Despite limitations due to the retrospective study, these results are consistent with controlled trials efficacy data. Further studies are required to assess the clinical significance and long-term prognosis of sustained dupilumab-induced hypereosinophilia.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Asma/tratamento farmacológico , Índice de Gravidade de Doença , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/sangue , Asma/fisiopatologia , Feminino , Seguimentos , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Introduction and gradual incremental escalation of a low dose of baked milk may accelerate the resolution of severe cow's milk (CM) allergy for some children. The purpose of our study was to evaluate the efficacy and safety of baked milk oral immunotherapy (OIT) in children with CM allergy after a low-dose baked milk oral food challenge (OFC). METHODS: In a retrospective analysis of OFC performed between 2013 and 2018 at the Children's Hospital of Toulouse (France), we identified 64 children with CM allergy and high milk and casein-specific IgE levels, who underwent a total of 171 milk OFC. Mean age at 1st OFC was 4.8 years. Mean CM-specific IgE was 47.9 kUA/L, and mean casein-specific IgE was 42.3 kUA/L. RESULTS: Most children were treated with baked milk OIT. Our study shows that 67.2% of the children did not react to 1st low-dose baked milk OFC (168.6 mg of CM protein). Eighteen percent of children stopped the OIT at home. Finally, desensitization to fresh milk was achieved in 27 children (42.2% of children allergic to CM). Children with lower CM-specific IgE levels have a significantly higher probability of becoming desensitized to unbaked CM. CONCLUSION: Most children with CM allergy and high milk and casein-specific IgE levels tolerate the introduction of baked milk. However, the occurrence of anaphylactic reactions during OIT remains possible.
Assuntos
Dessensibilização Imunológica/métodos , Hipersensibilidade a Leite/terapia , Leite/imunologia , Administração Oral , Adolescente , Alérgenos/administração & dosagem , Alérgenos/imunologia , Anafilaxia/epidemiologia , Anafilaxia/imunologia , Animais , Caseínas/imunologia , Criança , Pré-Escolar , Culinária/métodos , Feminino , França , Temperatura Alta , Humanos , Imunoglobulina E/imunologia , Lactente , Masculino , Leite/efeitos adversos , Hipersensibilidade a Leite/imunologia , Estudos RetrospectivosRESUMO
BACKGROUND: Chronic cough management is challenging as this condition is often associated with multiple comorbidities, requiring a multidisciplinary diagnostic approach. Little is known about the characteristics of obese patients with chronic cough. This study aims to describe treatable traits of chronic cough and the response to pump proton inhibitor (PPI) therapy in this sub-group of patients. METHODS: A retrospective, observational study was performed in patients with chronic cough in a French University Hospital. Characteristics of chronic cough were analyzed for obese (N = 112) and non-obese (N = 355) patients. Refractory cough was estimated at 6 and 12 months. RESULTS: The 3 main treatable traits associated with chronic cough in obese patients and non-obese patients were gastroesophageal reflux disease (GERD), asthma, and upper airway cough syndrome (UACS). A noticeable difference was the higher frequency of GERD (47.3% vs 34.6%, p = 0.0188) and obstructive sleep apnea (OSA) (9.8% vs 3.1%, p = 0.0080) in obese patients compared to non-obese patients. Pump proton inhibitor (PPI) treatment had a significantly higher success rate in obese patients (32.5% vs 17.0%, p < 0.05) and refractory cough at 12 months was less frequently reported in obese patients (22.3% vs 34.1%, p < 0.05). CONCLUSION: In a context of chronic cough, a higher prevalence of GERD was noted in obese patients compared to non-obese patients and obese patients were more responsive to PPI treatment. Moreover, OSA was reported more frequently as a treatable trait in obese patients and should be considered early in the diagnostic evaluation. Prospective clinical studies that evaluate the contribution of obesity to chronic cough are further needed.
Assuntos
Tosse/complicações , Refluxo Gastroesofágico/tratamento farmacológico , Obesidade/complicações , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Doença Crônica , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Anatomically complex airway stenosis (ACAS) represents a challenging situation in which commercially available stents often result in migration or granulation tissue reaction due to poor congruence. This proof-of-concept clinical trial investigated the feasibility and safety of computer-assisted designed (CAD) and manufactured personalised three-dimensional (3D) stents in patients with ACAS from various origins. After CAD of a virtual stent from a CT scan, a mould is manufactured using a 3D computer numerical control machine, from which a medical-grade silicone stent is made. Complication rate, dyspnoea, quality of life and respiratory function were followed after implantation. The congruence of the stent was assessed peroperatively and at 1 week postimplantation (CT scan). The stent could be implanted in all 10 patients. The 3-month complication rate was 40%, including one benign mucus plugging, one stent removal due to intense cough and two stent migrations. 9 of 10 stents showed great congruence within the airways, and 8 of 10 induced significant improvement in dyspnoea, quality of life and respiratory function. These promising outcomes in highly complex situations support further investigation on the subject, including technological improvements.â TRIAL REGISTRATION NUMBER: NCT02889029.
Assuntos
Obstrução das Vias Respiratórias/terapia , Desenho de Prótese , Stents , Obstrução das Vias Respiratórias/etiologia , Brônquios/patologia , Desenho Assistido por Computador , Constrição Patológica/etiologia , Constrição Patológica/terapia , Dispneia/etiologia , Dispneia/terapia , Humanos , Transplante de Pulmão/efeitos adversos , Estudo de Prova de Conceito , Qualidade de Vida , Stents/efeitos adversos , Inquéritos e Questionários , Tomografia Computadorizada por Raios X , Traqueia/patologia , Traqueobroncomalácia/complicaçõesRESUMO
We report a case of thoracic air-leak syndrome, an extremely rare complication developed after an episode of organizing pneumonia due to graft-vs-host disease in a 19-year-old male. This unusual non-infectious pulmonary complication occurred 527 days after allogeneic HSCT and led to the patient's death within 1 month due to cardio-respiratory failure. Herein, we highlight chest-imaging aspects which are typical. Early detection by high-resolution chest CT could improve patient management.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pneumotórax/etiologia , Evolução Fatal , Humanos , Masculino , Pneumotórax/diagnóstico por imagem , Pneumotórax/terapia , Síndrome , Fatores de Tempo , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
The authors report their findings regarding lung ultrasound profiles in a population of transplant recipients. Twenty-two patients were studied once each in multiple different ultrasound windows focusing on pleural, lung, and diaphragmatic signatures. All studies were performed in presumably otherwise healthy recipients at an outpatient follow-up visit at least 3 months after transplantation. Those with recent pulmonary infections or decline in lung function were excluded from enrollment. The majority of scans revealed otherwise normal lungs with lung sliding, but there were more abnormalities than one would expect in a healthy control group. Lung ultrasonography will likely never replace other cross-sectional imaging given its inherent visual limitations but adds another modality to interrogate the lung/pleural interface and diaphragmatic function.
Assuntos
Transplante de Pulmão , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , TransplantadosRESUMO
BACKGROUND: Cardiac output (CO) is a prognostic factor in pulmonary hypertension (PH). Right heart catheterisation using the direct Fick method or thermodilution (TD) is the reference technique for CO measurement. Impedance cardiography (IPc) is a known non-invasive method of measuring CO. OBJECTIVES: In our study, we assume that the measurement of CO by IPc using the PHYSIOFLOW® system is as accurate as TD or using the direct Fick method in patients with PH in group 1 or group 4. METHODS: A total of 75 patients were enrolled in a prospective study carried out at the hypertension reference centre of Toulouse University Hospital. Right heart catheterisation was performed for the diagnosis or follow-up of the disease. CO was measured using the Fick method, TD, and IPc simultaneously. A Bland-Altman analysis was plotted. RESULTS: CO was 5.7 ± 1.9 L/min as measured by the Fick method, 5.4 ± 1.5 L/min by TD, and 5.5 ± 1.7 L/min by IPc. The bias between CO measurements by IPc and the direct Fick method was 0.149 L/min (95% CI, -0.298 to 0.596). The bias between CO measurements by IPc and the TD method was -0.153 L/min (95% CI, -0.450 to 0.153). The correlation decreased with the more extreme CO values (< 3 L/min or > 7 L/min). A few factors changed the agreement between measurements (BMI or membership in group 4). CONCLUSION: To conclude, this study shows that the measurement of CO by IPc in PH patients is reliable compared to the direct Fick method and TD obtained by right heart catheterisation. This accuracy decreases for extreme CO values.
Assuntos
Débito Cardíaco , Cardiografia de Impedância , Hipertensão Pulmonar/fisiopatologia , Idoso , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , TermodiluiçãoRESUMO
BACKGROUND: Untreated Obstructive Sleep Apnea Hypnopnea Syndrome (OSAHS) is a known factor contributing to resistant hypertension (HT). Continuous Positive Airways Pressure (CPAP) is effective to decrease blood pressure (BP) in severe OSAHS. In our clinical practice, hypertensive patients seem less symptomatic with regard to severe OSAHS than normotensive patients, leading to a risk of underdiagnosis when OSAHS is screened with Epworth Sleepiness Scale (ESS). We aimed to confirm that severe OSAHS is less symptomatic in HT patients than normotensive patients using ESS. METHODS: We retrospectively compared two age, gender-matched groups - 100 hypertensive patients and 100 normotensive patients - with severe OSAHS defined as an AHI (Apnea Hypopnea Index) ≥30. OSAHS was considered symptomatic when ESS > 10. RESULTS: The two groups of patients did not differ significantly with respect to main characteristics including Body Mass Index (BMI), AHI and ODI (Oxygen Desaturation Index). Systolic and Diastolic BP were higher in HT patients (p < 0.01). HT patients were less symptomatic with regard to severe OSAHS with a lower ESS (10.0 vs 11.9, p < 0.01), and a lower number of patients with an ESS > 10 (30% vs 58%, p < 0.01). In multivariable analysis adjusted on age, gender, Obesity, Systolic BP, Diastolic BP, AHI and ADO, normotension was significantly associated with symptomatic OSAHS (OR = 2.83, [1.298-6.192], p < 0.01). CONCLUSIONS: In our study on patients with severe OSAHS, ESS score was lower in hypertensive patients than in normotensive patients. This discrepancy may lead to an underestimation of severe OSAHS in hypertensive patients.
Assuntos
Hipertensão/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Feminino , França , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polissonografia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Asthma affects between 3% to 8% of pregnant women. Previous studies have suggested that women's prescriptions for asthma medications change during pregnancy. The aim was to describe the prescription of asthma medications before and during pregnancy in France. METHODS: Women from the EFEMERIS, a French database assessing the drugs prescribed, dispensed and reimbursed during pregnancy, delivering between July 2004 and December 2012, were included. Women, who were dispensed asthma medications on at least two dates from 3 months prior to pregnancy through delivery, were considered. RESULTS: 2,977 women out of 69,205 (4%) were selected. They were prescribed 2.4 ± 1.2 different anti-asthmatic drugs with 3.5 ± 2.7 different dispensing dates. Almost 62% of the women were dispensed at least one prescription for short-acting ß2-agonist (SABA), 63% at least one inhaled corticosteroid (IC), 42% a fixed-combination of an IC and a long-acting ß2-agonist (LABA) and 8% a LABA. An increase in SABA and IC prescriptions and a decrease in fixed-combination prescriptions were observed during pregnancy compared to pre-pregnancy period. A rapid drop in prescriptions for montelukast was observed. Among the 1,507 women who were prescribed asthma medication before pregnancy, one third had a drop in dispensed asthma medications from the beginning of pregnancy. CONCLUSIONS: The prevalence of dispensed asthma medications varies during pregnancy. There is a decrease in the prescriptions of fixed-combinations during pregnancy and an increase in the prescriptions of ICs. It appears important to study the potential impact of such changes on fetuses and newborns.
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Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Bases de Dados Factuais/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Antiasmáticos/administração & dosagem , Combinação de Medicamentos , Feminino , França/epidemiologia , HumanosRESUMO
Dyspnoea is a prominent symptom of chronic obstructive pulmonary disease (COPD). Recent multidimensional dyspnoea questionnaires like the Multidimensional Dyspnea Profile (MDP) individualise the sensory and affective dimensions of dyspnoea. We tested the MDP in COPD outpatients based on the hypothesis that the importance of the affective dimension of dyspnoea would vary according to clinical characteristics.A multicentre, prospective, observational, real-life study was conducted in 276 patients. MDP data were compared across various categories of patients (modified Medical Research Council (mMRC) dyspnoea score, COPD Assessment Test (CAT) score, Global Initiative for Chronic Obstructive Lung Disease (GOLD) airflow obstruction categories, GOLD "ABCD" categories, and Hospital Anxiety and Depression Scale (HADS)). Univariate and multivariate regressions were conducted to explore factors influencing the affective dimension of dyspnoea. Cluster analysis was conducted to create homogeneous patient profiles.The MDP identified a more marked affective dimension of dyspnoea with more severe mMRC, CAT, 12-item Short-Form Health Survey mental component, airflow obstruction and HADS. Multivariate analysis identified airflow obstruction, depressive symptoms and physical activity as determinants of the affective dimension of dyspnoea. Patients clustered into an "elderly, ex-smoker, severe disease, no rehabilitation" group exhibited the most marked affective dimension of dyspnoea.An affective/emotional dimension of dyspnoea can be identified in routine clinical practice. It can contribute to the phenotypic description of patients. Studies are needed to determine whether targeted therapeutic interventions can be designed and whether they are useful.
Assuntos
Dispneia/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Análise por Conglomerados , Depressão/complicações , Dispneia/diagnóstico , Feminino , Volume Expiratório Forçado , França , Humanos , Pulmão/fisiopatologia , Pneumopatias Obstrutivas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pacientes Ambulatoriais , Fenótipo , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Fumar , Inquéritos e Questionários , Fatores de TempoAssuntos
Asma , Termoplastia Brônquica , Brônquios/cirurgia , Broncoscopia , Temperatura Alta , HumanosRESUMO
BACKGROUND: Salbutamol abuse detection by athletes is based on a urinary upper threshold defined by the World Anti-Doping Agency (WADA). However, this threshold was determined in healthy, untrained individuals and after a dose of salbutamol inhaled that might not really mirror the condition of asthmatic athletes and the experts's guidelines for asthma management. We aimed to revise this threshold in accordance with recommended clinical practice (that appear to be different from the actual WADA recommendation) and in exercise conditions. METHODS: For the present open-label design study, we included 12 trained male cyclists (20 to 40 y/o) with asthma. Differently from the previous pharmacokinetic study supporting the actual salbutamol urinary upper threshold, we decided to administer a close to recommended clinical practice daily dose of 3x200 µg.d(-1) inhaled salbutamol (instead of 1600 µg.d(-1) as authorized by the anti-doping policy). Urine salbutamol concentration was quantified by liquid chromatography-tandem ion trap mass spectrometry and corrected for urine density, at rest and after a 90-min cycling effort at 70-80 % of the maximal aerobic power. RESULTS: The maximum urine salbutamol concentration value peaked after the cycling effort and was 510 ng.mL(-1). That is twice lower than the actual WADA threshold to sanction salbutamol abuse, this "legal" threshold being based on pharmacokinetic data after a daily dose that is 8 fold the total dose sequentially administrated in our study. Considering its 95 % confidence interval, this threshold value could be more stringent. CONCLUSION: By using conditions in accordance with the experts' clinical and safety guidelines for asthma management in athletes undergoing an intense exercise bout, our study suggests that the urine salbutamol concentration threshold could be lowered to redefine the rule supporting the decision to sanction an athlete for salbutamol abuse.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Albuterol/administração & dosagem , Asma/tratamento farmacológico , Ciclismo , Broncodilatadores/administração & dosagem , Dopagem Esportivo/legislação & jurisprudência , Formulação de Políticas , Administração por Inalação , Agonistas de Receptores Adrenérgicos beta 2/farmacocinética , Agonistas de Receptores Adrenérgicos beta 2/urina , Adulto , Albuterol/farmacocinética , Albuterol/urina , Asma/diagnóstico , Asma/fisiopatologia , Broncodilatadores/farmacocinética , Broncodilatadores/urina , Cromatografia Líquida , Esquema de Medicação , Humanos , Masculino , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem , Resultado do Tratamento , Urinálise , Adulto JovemRESUMO
BACKGROUND: House dust mite (HDM) immunotherapy has proven efficacy in treating allergic rhinitis (AR) symptoms. This trial evaluated the dose-response relationship of SLIToneULTRA® HDM mix based on immunological parameters and safety in subjects with moderate-to-severe HDM AR not controlled by symptomatic medication. MATERIALS AND METHODS: A randomized, parallel-group, open-label, clinical trial compared 50/150/300 standard reactivity unit (SRU) doses of SLIToneULTRA® HDM mix for 6 months. Subjects had moderate-to-severe HDM AR, positive skin prick and IgE against Dermatophagoides pteronyssinus/Dermatophagoides farinae (DP/DF). The primary end point was change from baseline in the IgE-blocking factor against DP after 6 months. Secondary end points measured changes in the IgE-blocking factor for DP at 3 months and for DF at 3 and 6 months, and in IgG4 and specific IgE to DP/DF after 3 and 6 months. Tolerability was assessed through the evaluation of all adverse events (AEs). RESULTS: A total of 219 subjects were randomized and 196 completed the trial. Dose effect was significant on DP IgE-BF after 6 months (p = 0.018). The change in the DP IgE-blocking factor at a 300-SRU dose was higher than at other doses after 3 (p = 0.008) and 6 (p = 0005) months of treatment. Similar changes were observed for IgG4 and allergen-specific IgE. The number of AEs increased with the dose and were mild-to-moderate, with no severe treatment-related AEs reported. The most frequent AEs were oral/tongue pruritus, mouth oedema and abdominal upper pain. CONCLUSIONS: Data showed a dose-response for immunological markers and safety with a better immunological response for 300 SRU. The highest dose (300 SRU daily) was considered as the optimal maintenance dose.
Assuntos
Antígenos de Dermatophagoides/imunologia , Dessensibilização Imunológica , Rinite Alérgica/terapia , Adulto , Animais , Dessensibilização Imunológica/efeitos adversos , Relação Dose-Resposta Imunológica , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Rinite Alérgica/imunologiaRESUMO
BACKGROUND: Continuous Positive Airway Pressure (CPAP) remains the reference treatment for moderate to severe forms of the Sleep Apnea/Hypopnea Syndrome (SAHS). Compliance to the treatment appears to be a key factor to improving health status of these patients. METHODS: We conducted a multicenter, prospective, randomized, controlled, parallel group trial of standard support completed or not within 3 months of coaching sessions for newly diagnosed SAHS patients starting CPAP therapy. This study has been recorded by AFSSAPS with the RCB number: 2009-A01127-50 and received favourably by the Human Studies Committee in France. The coaching session consisted of 5 sessions of telephone-based counselling by competent staff. The primary outcome was the proportion of patients using CPAP more than 3 h per night for 4 months; the secondary outcome was mean hours of CPAP usage in the 2 groups. RESULTS: Three hundred and seventy-nine patients fulfilled the inclusion criteria and were randomized. The percentage of patients using CPAP more than 3 h per night for 4 months was 65 % for the standard support group and 75 % for the coached group. This difference reached a statistical significance (χ2 = 3.97). The mean CPAP usage was increased in the coached group versus standard group. A difference of 26 min was observed (4 h34+/-2 h17 and 4 h08+/-2 h25 respectively, p = 0.04). CONCLUSION: This study shows that SAHS patients who benefit from phone coaching are statistically more compliant to CPAP than a standard support group is. A simple phone coaching procedure based on knowledge of the disease and reinforcement messages about treatment benefits helps to improve CPAP adherence in SAHS patients. TRIAL REGISTRATION: NCT02435355.