Obstructive Sleep Apnea: a risk for uncontrolled and more severe asthma in adults that we should keep an eye on.

Summary: Background. Asthma control can be influenced by several factors, including obstructive sleep apnea (OSA). The literature reports variable prevalence and magnitude of OSA impact on asthma outcomes. The aim of our study is to analyze the frequency of high-risk for OSA in asthma patients and its impact on disease severity and control. Methods. We conducted a cross-sectional study at an Allergy Department with adult asthma patients recruited while undergoing routine lung function tests. Data on sex, age, body mass index, allergen sensitization, smoking habits, risk of OSA (using the Berlin questionnaire), rhinitis control (through CARAT), asthma severity (based on GINA 2023), asthma control (using the ACT), adherence to asthma treatment (through Treatment Adherence Measure) and pulmonary function test results were collected. Results. We included 216 patients, predominantly women (70.4%), with a median (P25-P75) age of 29.0 (21.0-45.0) years, of whom 28.2% were on GINA treatment levels 4-5. In 75.5% of cases asthma was controlled. High-risk for OSA was identified in 21.8% of patients. Asthma patients with high-risk for OSA were more likely to have uncontrolled [(47.8%; n = 22) vs (15.8%; n = 26); p less than 0.001] and more severe disease [(44.7%; n = 21) vs (23.7%; n = 40), p = 0.006]. In multivariable analysis, high-risk for OSA (OR 2.81 [95%CI 1.1.28-6.17], p = 0.010), sex (women) (OR 5.21 [95% CI 1.70-15.96], p = 0.004), uncontrolled rhinitis (OR 3.65 [95%CI 1.38-9.64], p = 0.009) and GINA asthma treatment steps 4-5 (OR 2.46 [95%CI 1.15-5.26], p = 0.020) were associated with uncontrolled asthma. Conclusions. It is crucial to actively investigate OSA, especially in patients with uncontrolled and more severe forms of asthma.

The impact of a drug allergy label in an internal medicine ward.

Summary: Background. Drug hypersensitivity reactions are presumably immune-mediated reactions that cause reproducible signs and/or symptoms. Overdiagnosis of drug allergy, frequently self-reported, is common and carries significant limitations. We intended to analyze the frequency and impact of drug allergy in hospitalized patients. Methods. A retrospective study was conducted in an Internal Medicine ward at a tertiary hospital in Portugal. All patients with a drug allergy report admitted within a 3-year period were included. Data were collected from their electronic medical records. Results. We found that 15.4% of patients had a report of drug allergy, with antibiotics being the most common (56.4%), followed by non-steroidal anti-inflammatory drugs (21.7%) and radiocontrast media (7.0%). The allergy report affected the clinical approach of 14.5% of patients by motivating the use of second-line agents, or the eviction of necessary procedures. The usage of alternative antibiotics entailed a cost increase of 2.4 times. There were 14.7% of patients to whom the suspected drug was administered: 87.0% tolerated and 13.0% developed a reaction. Only 1.9% were referred to our Allergy and Clinical Immunology department and proceeded in their allergy study. Conclusions. In this study, a considerable number of patients had a drug allergy label on their records. This label contributed to an increase in the cost of treatment, or the avoidance of necessary exams. However, disregarding an allergy record may lead to potentially life-threatening reactions that proper risk assessment could avoid. Further investigation should always be part of the follow-up routine of these patients, and better articulation between departments should be encouraged.

Immunoallergic disorders in the elderly.

Summary: Although allergic diseases have become increasingly prevalent in the elderly, there are few data on this population. Through a retrospective analysis of the electronic medical records of patients aged 65 years and above followed in our Immunoallergology Unit, we aimed to characterize the immunoallergic diseases of the elderly. The most common disorders were respiratory diseases (n = 185; 50%), mucocutaneous diseases (n = 113; 31%), drug allergy (n = 31; 8%), food allergy (n = 9; 2%), and anaphylaxis (n = 9; 2%). Use of specific immunotherapy was residual (n = 2; 1%). There was an association between anaphylaxis and both, drug (p = 0.004) and food (p = 0.013) allergies. Non-allergic rhinitis and bronchial asthma were more frequent in females, and ACE inhibitors/ARB induced-angioedema in males. Recognizing the characteristics of immunoallergic diseases in the elderly and the specificities of this age group is paramount in providing these patients with the best possible care.

Factors Associated With Asthma Control in 121 Preschool Children.

BACKGROUND AND OBJECTIVES: Data on risk factors for uncontrolled asthma in preschool children are controversial. Objective: This study aims to explore the association between clinical and functional parameters and the lack of asthma control in preschool children. METHODS: Children aged 3-5 years with asthma and healthy controls were recruited. A questionnaire was used to identify potential risk factors for uncontrolled asthma, as defined by the Global INitiative for Asthma criteria. Lung function and bronchial reversibility were evaluated through impulse oscillometry and spirometry. Adjusted odds ratios were estimated based on multivariable generalized additive regression models. The discriminative ability of the models was measured by the area under the receiver operating characteristic curve (AUC). RESULTS: The study population comprised 121 children (107 with asthma and 14 healthy controls). Fifty-three patients (50%) had uncontrolled asthma. After adjustment, the variables associated with an increased risk of lack of control were as follows: "More than 3 flare-ups in the last 12 months", "Moderate to severe rhinitis", and "Relative variation in postbronchodilator FVC and FEV1". The AUC of the final models that included variation in FVC or FEV1 were 0.82 and 0.81, respectively. The R5-20, R5-20%, and AX z-score values of the healthy group were lower than those of children with asthma. CONCLUSION: In preschool children, clinical and functional parameters are associated with uncontrolled asthma. More studies are needed to confirm the usefulness of impulse oscillometry.

Molecular Profile of Sensitization to Dermatophagoides pteronyssinus Dust Mite in Portugal.

BACKGROUND AND OBJECTIVES: To analyze component-resolved diagnosis of sensitization to Dermatophagoides pteronyssinus (Der p) in patients with respiratory allergy and the association between diagnostic findings and clinical severity in different geographical areas. METHODS: The study population comprised 217 patients (mean age, 25.85 [12.7] years; 51.16% female) selected from 13 centers in Portugal (5 from the North, n=65). All had allergic rhinitis with or without asthma and positive skin prick test results to at least 1 dust mite. Specific IgE (sIgE) to Der p, Dermatophagoides farinae, Lepidoglyphus destructor, Der p 1, Der p 2, Der p 10, and Der p 23 was determined using ImmunoCAP. The Mann-Whitney test was applied for the following comparisons: rhinitis vs rhinitis and asthma; mild vs moderate-to-severe rhinitis; North vs South. RESULTS: The prevalence of sensitization was 98.2% for Der p, and 72.4%, 89.4%, 9.7%, and 77% for Der p 1, Der p 2, Der p 10, and Der p 23, respectively. The corresponding median sIgE levels were 8.56, 17.7, 0.01, and 3.95 kUA/L. sIgE to all allergens was higher in patients with moderate-to-severe rhinitis and rhinitis with asthma (nonsignficant). Concentrations of sIgE to Der p 2 were significantly higher in the South than in the North (P=.0496). CONCLUSION: The most common sensitization in Portugal was to Der p. The highest prevalence and median sIgE level were observed for Der p 2. All sIgE values for molecular components were higher in more symptomatic patients (nonsignificant). Concentrations of sIgE to Der p 2 were higher in the South, probably because of the warmer temperature and/or the larger sample size.

Cross-cultural validation of the Portuguese from Portugal version of the Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire.

SUMMARY: Introduction. The Test for Respiratory and Asthma Control in Kids (TRACK) is a tool to assess asthma control in preschool children. This study aims to validate the Portuguese from Portugal version of the TRACK questionnaire. Methods. A prospective cohort study was carried out to assess their psychometric characteristics. Caregivers of 141 children under age 5 with asthma symptoms were enrolled. Results. Internal reliability was close to 0.70 (Cronbach's α). The test-retest reliability was 0.87. TRACK scores were different between well, partially, and non-controlled asthma groups (p less than 0.001). Patients rated as having better control showed an increase in TRACK scores. Conclusions. The Portuguese version of the TRACK questionnaire is accurate and reliable for monitoring asthma control. Its use may help to overcome challenges with the management of this age group.

Blood or skin: what is best in predicting cow's milk allergy diagnosis?

Summary: Cut-off values for both skin prick tests (SPT) and specific IgE (sIgE) levels for predicting cow´s milk allergy (CMA) diagnosis are not universally defined. This study is a retrospective analysis of consecutive children (0-18 years-old) with suspected CMA tested with SPT and sIgE for cow's milk (CM) and its fractions between 2016-2017. CMA diagnosis was defined by a positive oral food challenge or a highly suggestive clinical history of CMA and SPT and/or sIgE positive to CM and/or its fractions. One hundred and five patients were included, 58% males with a median age of 2.5 (P25-P75:1-6) years and the diagnosis was confirmed in 83 patients (79%). The variables associated with CMA diagnosis were SPT with CM (p minor 0,05) and casein (p minor 0,05) and all sIgE to CM and its fractions (alfa Lactalbumin, beta Lactoglobulin and casein; p minor 0,05 for all). Optimal cut39 off points (Youden's index) for CMA diagnosis were, for the mean wheal diameter, to CM milk of 4.5mm and to casein of 3mm. For sIgE levels the optimal cut-off points were: for CM of 4.36 kUA/L, alfa-lactalbumin of 1.6 kUA/L, beta-lactoglobulin of 1.7 kUA/L and for casein of 2.6 kUA/L. The role of SPT and sIgE levels to cow´s mlik and its fractions is unequivocal in CMA follow-up. Moreover, sIgE levels seem to be more discriminatory than SPT.

Asthma and COPD "overlap": a treatable trait or common several treatable-traits?

Summary: In the last years, disease classification of chronic respiratory diseases (CRD) has been vivaciously discussed and new concepts have been introduced, namely asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). Controversially the GOLD consensus document of 2020 considered that we should no longer refer to ACO, as they constitute two different diseases that may share some common traits and clinical features. The treatable traits approach has numerous strengths that are applicable to several levels of health care. In this paper we review the application of the treatable traits to CRD and describe in detail the ones already identified in patients with asthma and COPD. Treatable traits in CRD can be divided in pulmonary, extra-pulmonary and behavior/lifestyle risk factors. Patients with both asthma and COPD patients have clearly recognized treatable traits in all these subtopics but it is notorious the severe and frequent exacerbations, the associated cardiovascular disease and the low health related quality of life and productivity of these patients.

Patch testing in a case of eslicarbazepine and carbamazepine induced cutaneous reaction.

Summary: Anticonvulsants are among the drugs most commonly involved in cutaneous adverse drug reactions (CADRs). Eslicarbazepine is a new anti-epileptic drug, chemically related to carbamazepine but with a more favorable safety profile. We report the clinical case of a woman who developed a skin rash on day 10 of eslicarbazepine with further exacerbation with eosinophilia on day 2 of carbamazepine. Epicutaneous tests were positive with eslicarbazepine.

Piperacillin-tazobactam anaphylaxis: a rare cause of occupational disease.

Summary: Piperacillin is a beta-lactam antibiotic of penicillin family. Some penicillins were report-ed as occupational diseases cause, but piperacillin anaphylaxis with occupational sensi-tization is rare. We describe the case of a female nurse with recurrent anaphylaxis in last few months without apparent cause, only in work environment. Latex allergy was excluded after negative latex glove provocation. Later during diagnostic workup, the patient reported a similar reaction minutes after piperacillin preparation. She denied any previous antibiotic therapeutic exposure. Skin prick tests (SPT) to beta-lactams were positive to piperacillin, penicillin G and major and minor determinants. SPT to cefuroxime was negative but intradermic test was positive. The patient has indication for beta-lactams eviction and for adrenaline auto-injector kit. No further reactions occurred after patient's transfer to another department with minimum possible exposure. Allergic risk prevention is essential and must be rapidly implemented to avoid incapacitating occupational diseases development.

Non-steroidal anti-inflammatory drug hypersensitivity in children.

INTRODUCTION: There are rather few publications about hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAID) in the paediatric age. In this study, we aimed to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID in order to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the factors associated with confirmed NSAID hypersensitivity. METHODS: We conducted a retrospective analysis of the clinical files from every patient under 18 years old who attended two Portuguese paediatric allergy outpatient clinics, from January 2009 to August 2014, due to a suspected NSAID hypersensitivity. RESULTS: We included 119 patients, with a median age of nine years (P25-P75: 5-14). Ibuprofen was the commonest implicated NSAID in the patients' reports (n=94-79%). After DPT, NSAID hypersensitivity was confirmed in nine (7.6%) patients, excluded in 93 (78.2%) and was inconclusive in 17 (14.3%). In the majority (n=95-79.8%), the reaction occurred in the first 24h after intake. Eighty-four patients (70.6%) reported only cutaneous manifestations and 18 (15.1%) had systemic symptoms. Anaphylaxis represented a relative risk to NSAID hypersensitivity confirmation. No association was found for atopy and the number of previous reactions. CONCLUSION: In our study, NSAID hypersensitivity was confirmed in a small proportion of the patients with a previous reported reaction. Ibuprofen was the most implicated drug with urticaria/angio-oedema as the commonest manifestation. Anaphylaxis was associated with confirmed drug hypersensitivity. The drug provocation test was essential to establish the diagnosis.

Diagnosis of eosinophilic esophagitis in an infant undergoing milk oral immunotherapy - a case report.

Although the standard of care for cow's milk (CM) allergy is strict food avoidance, oral immunotherapy (OIT) is being widely investigated as an alternative management option in certain cases. Immediate adverse reactions to OIT have been described, but its long-term effects are much less often reported. We present the case of a girl diagnosed with IgE-mediated CM allergy that was proposed for our CM OIT protocol at the age of 3 years. The first sessions (dose escalation up to 5 ml) were well tolerated, however eight hours after her daily morning dose of 5 ml CM the child developed late episodes of vomiting. No other symptoms, particularly immediately after CM ingestion, were reported. These episodes became progressively worse and on the third day she presented mild dehydration and blood eosinophilia. After OIT interruption, a progressive clinical improvement was observed. An esophageal endoscopy was performed, showing signs of eosinophilic esophagitis (EoE) with peak 20 eosinophils/hpf. After treatment with topical swallowed fluticasone (500 mcg bid) and a CM-free diet for 4 months, the child was asymptomatic and endoscopy and biopsy findings were normal.The long-term effects of milk OIT are still in part unknown. We hypothesize that eosinophilic esophagitis may have been a consequence of OIT in this case. The findings seem to indicate that food allergy may play a role in the pathogenesis of esophageal eosinophilia and stress the importance of a well programmed long-term follow-up of patients that have undergone milk OIT.

Cystic fibrosis, atopy, asthma and ABPA.

The role of atopy on cystic fibrosis (CF) progression remains unclear but evidence suggests that it may influence the appearance of co-morbid conditions such as CF asthma or allergic bronchopulmonary aspergillosis (ABPA). Recognising asthma in patients with CF is not always easy but the identification of atopic markers favours the diagnosis. Physicians should be aware of this fact in order to achieve a better control of respiratory symptoms in patients with CF. Bronchial mucosa inflammation and abnormal mucus predispose to mould colonisation. These patients are at higher risk of allergic sensitisation, especially when atopic susceptibility is present. In the particular case of A. fumigatus, allergic sensitisation precedes ABPA development, which occurs in up to 10% of CF patients. Progression of lung function deterioration is most strikingly pronounced in patients with ABPA. Therefore, sensitisation with A. fumigatus should be regularly tested in patients with CF, especially those at higher risk. Recombinant allergens constitute an important advance in differentiating Aspergillus sensitisation from ABPA itself.

Drug provocation tests to betalactam antibiotics: experience in a paediatric setting.

BACKGROUND: Few studies have been performed in children with suspected betalactam allergy. We aimed to assess the role of the drug provocation test (DPT) with betalactams in a paediatric setting and to study the association between allergy to betalactam antibiotics and other allergic diseases. METHODS: We included all the patients under 15 years old who were consecutively referred to the Immunoallergy Department, Dona Estefânia Hospital, Portugal (January 2002 to April 2008) for a compatible history of allergic reaction to betalactam. All were submitted to a DPT. Children were proposed to perform skin tests (ST) to betalactam antibiotics followed by DPT. If they decline ST, a DPT with the culprit drug was performed. RESULTS: We studied 161 children, 60% were boys, with a median age of 5 years old at the time of the DPT. Thirty-three patients (20.5%) had an immediate reaction and 33 (20.5%) a non-immediate reaction. The severity of the reported reactions was low in most cases. Skin tests to betalactams were performed in 47 children and were positive in 8. DPT was positive in only one (3.4%) of the patients skin tested and in 11 (13.4%) of those not skin tested. The severity of the DPT reaction was low. Asthma and food allergy were associated with a positive DPT in the later group. CONCLUSIONS: DPT seems a safe procedure even in the absence of ST in non-severe cases. This could be a practical option in infants and pre-school children, where ST are painful and difficult to perform. Additional caution should be taken in children with asthma and food allergy.

Lung function and clinical risk factors for asthma in infants and young children with recurrent wheeze.

BACKGROUND: Although several risk factors for asthma have been identified in infants and young children with recurrent wheeze, the relevance of assessing lung function in this group remains unclear. Whether lung function is reduced during the first 2 years in recurrently wheezy children, with and without clinical risk factors for developing subsequent asthma (ie, parental asthma, personal history of allergic rhinitis, wheezing without colds and/or eosinophil level >4%) compared with healthy controls was assessed in this study. METHODS: Forced expiratory flows and volumes in steroid naïve young children with >or=3 episodes of physician confirmed wheeze and healthy controls, aged 8-20 months, were measured using the tidal and raised volume rapid thoracoabdominal compression manoeuvres. RESULTS: Technically acceptable results were obtained in 50 wheezy children and 30 controls using tidal rapid thoracoabdominal compression, and 44 wheezy children and 29 controls with the raised volume technique. After adjustment for sex, age, body length at test and maternal smoking, significant reductions in z scores for forced expiratory volume at 0.5 s (mean difference (95% CI) -1.0 (-1.5 to -0.5)), forced expired flow after 75% forced vital capacity (FVC) has been exhaled (FEF(25)) (-0.6 (-1.0 to -0.2)) and average forced expired flow over the mid 50% of FVC (FEF(25-75)) (-0.8 (-1.2 to -0.4)) were observed in those with recurrent wheeze compared with controls. Wheezy children with risk factors for asthma (n = 15) had significantly lower z scores for FVC (-0.7 (-1.4 to -0.04)) and FEF(25-75) (-0.6 (-1.2 to -0.1)) than those without such risk factors (n = 29). CONCLUSIONS: Compared with healthy controls, airway function is reduced in young children with recurrent wheeze, particularly those at risk for subsequent asthma. These findings provide further evidence for associations between clinical risk factors and impaired respiratory function in early life.