The role of immunologic tests for subfertility in the clinical environment.

Unexplained subfertility and implantation failures not only are emotionally and physically distressing but also become a significant obstacle to reproductive-age couples who wish to build their family. Often, the currently recommended evaluation for these couples is significantly limited, and many of causes remain unexplained. To obtain an accurate diagnosis and treatment, proper evidence-based laboratory evaluation should be performed. Immune tests for women with subfertility and implantation failures are essential to recognize the immune etiology and appropriate therapeutic strategies. This review focuses on currently used immune tests for subfertile women.

Risk prediction of severe reaction to oral challenge test of cow's milk.

Cow's milk is one of the most common food allergens among children. Oral food challenge tests determine the threshold dose of allergens, but have not been standardized. To reduce the severe reactions, we developed a practical model of the test. We studied 111 high-risk patients who underwent a first milk oral food challenge on the risk-stratified dose between 2011 and 2017 for predicting the severe reaction risk. Severe reactions were defined as showing > 3 of Sampson's classification grade. Twenty-eight patients (25%) showed severe reactions without death. Prior to oral food challenge, severe reaction patients experienced milk avoidance (71% vs. 45%, p = 0.02) or bronchial asthma (61% vs. 28%, p = 0.003) more frequently and showed higher milk-specific IgE levels (median 28.3 vs. 7.7 UA/mL, p < 0.0001) than non-severe reaction patients. Multivariate logistic regression analyses established a formula including severe reaction-associated factors; increased levels of milk-specific IgE (odds ratio 11.61, p = 0.001), milk avoidance (odds ratio 3.88, p = 0.02), and bronchial asthma (odds ratio 3.75, p = 0.02). This model had 86% sensitivity and 56% specificity (cut-off 0.25) for risk. Five patients with < 25% probability developed severe reactions, which started in > 3 grade dyspnea up to 20 mL of challenge.Conclusion: This model could effectively reduce the severe reaction development on the first milk oral food challenge test according to the individual needs. What is Known: •Higher levels of milk-specific IgE values, bronchial asthma, and complete milk avoidance are independent risk factors of severe reactions during the cow's milk oral food challenge. What is New: •Statistical analyses of our milk oral food challenge records for 111 patients helped us develop a model formula predicting severe reactions at the first test with high specificity and sensitivity. •This simple risk-stratified protocol is useful for minimizing the adverse events in the first milk challenge.

Hypersensitivity reactions to beta-lactams in children.

PURPOSE OF REVIEW: To present the most recent evidence on beta-lactam hypersensitivity reactions in children. RECENT FINDINGS: Drug provocation tests (DPTs) are the gold standard when investigating beta-lactam allergy in children and evidence is increasingly supporting DPTs without skin tests as a safe approach when evaluating children with nonimmediate mild reactions to beta-lactams. Of note, data are limited in the adolescent population, and this attitude may not apply to this age group. Standardization of DPT protocols is required in nonimmediate reactions, as many protocols ranging from 1 to 10 days have been described. The optimal duration of DPT is still unknown, with extended protocols providing slightly more sensitivity and possible higher long-term compliance, at the expense of potential side effects associated with prolonged antibiotic use. On the other hand, 1-day DPTs will identify the vast majority of patients, and the rest will only develop a mild rash during a subsequent full treatment. The natural history of beta-lactam allergy in children is not well studied with recent evidence pointing to the resolution of most confirmed beta-lactam allergies after 3 years. SUMMARY: Further studies are needed for the standardization of DPT protocols and to confirm the favourable natural history of beta-lactam drug allergies in children. In addition, multicentric studies are required to confirm the increasingly accepted position of performing DPTs without skin tests in nonimmediate mild reactions to beta-lactams and to further evaluate the possibility of performing DPTs in benign immediate reactions to beta-lactams in children.

Oral food challenge using different target doses and time intervals between doses.

PURPOSE OF REVIEW: The oral food challenge (OFC) is a specific and vital tool used in clinical practice to identify the level of tolerance a person exhibits toward certain foods while diagnosing food-related allergies. OFC methods differ among countries. The aim of this review is to evaluate different target doses and determine the time interval between doses used for OFC. RECENT FINDINGS: We analyzed recent articles on target doses and time between doses, and noted that some papers reported low target doses and less time between doses. A low-dose OFC appears to be a useful strategy; a time interval of 15 min between doses is short and that of at least 1 h is appropriate. SUMMARY: Low-dose OFCs appear to be well tolerated and effective to avoid complete elimination of the consumption of foods causing allergies. For the safety of the OFC method, the time interval between doses should be more than 30 min.

Do Longer Intervals between Challenges Reduce the Risk of Adverse Reactions in Oral Wheat Challenges?

BACKGROUND: The use of oral food challenges (OFCs) in clinics is limited because they are complicated and associated with anaphylactic symptoms. To increase their use, it is necessary to develop novel, effective, and safe methods. However, the effectiveness of different OFCs has not been compared. OBJECTIVE: To investigate the effect of ingestion methods on wheat allergy symptoms and treatment during OFCs. METHOD: Without changing the total challenge dose, we changed the administration method from a 5-installment dose titration every 15 min (15-min interval method) to 3 installments every 30 min (30-min interval method). We retrospectively reviewed and compared the results of 65 positive 15-min interval wheat challenge tests conducted between July 2005 and February 2008 and 87 positive 30-min interval tests conducted between March 2008 and December 2009. RESULTS: A history of immediate symptoms was more common for the 30-min interval method; however, no difference between methods was observed in other background parameters. Switching from the 15-min to the 30-min interval method did not increase symptoms or require treatment. The rate of cardiovascular symptoms (p = 0.032), and adrenaline use (p = 0.017) was significantly lower with the 30-min interval method. The results did not change after adjusting for the effects of immediate symptom history in multivariate analysis. CONCLUSION: This study suggests that the 30-min interval method reduces the risk of adverse events, compared to the 15-min interval method.

Epinephrine use in positive oral food challenges performed as a screening test for food allergy therapy trials.

BACKGROUND: Previous studies report epinephrine use for positive oral food challenges (OFCs) to be 9-11% when generally performed to determine outgrowth of food allergies. Epinephrine use for positive OFCs performed as screening criteria for enrollment in therapeutic trials for food allergy has not been reported. OBJECTIVE: The objective of this study was to assess the characteristics and treatment for positive OFCs performed for screening subjects for food therapeutic trials. METHODS: Retrospective review of positive screening OFCs from 2 treatment trials, food allergy herbal formula-2 (n = 45) and milk oral immunotherapy (n = 29), conducted at the Icahn School of Medicine at Mount Sinai was performed. RESULTS: The most common initial symptom elicited was oral pruritus, reported for 81% (n = 60) of subjects. Overall, subjective gastrointestinal symptoms (oral pruritus, throat pruritus, nausea, abdominal pain) were most common (97.3% subjects), followed by cutaneous symptoms (48.7%). Of the 74 positive double-blind, placebo-controlled food challenge, 29 (39.2%) were treated with epinephrine; 2 of these subjects received 2 doses of epinephrine (6.9% of the reactions treated with epinephrine or 2.7% of all reactions). Biphasic reactions were infrequent, which occurred in 3 subjects (4%). CONCLUSIONS: Screening OFCs to confirm food allergies can be performed safely, but there was a higher rate of epinephrine use compared with OFCs used for assessing food allergy outgrowth. Therefore, personnel skilled and experienced in the recognition of early signs and symptoms of anaphylaxis who can promptly initiate treatment are required.

Anaphylaxis in the allergy practice.

BACKGROUND: Otolaryngologists managing patients with allergic rhinitis are faced with the possibility of anaphylactic reactions in the office, especially when providing allergen immunotherapy. METHODS: Literature review was performed and recent published articles on anaphylaxis were examined. Details on pathophysiology, incidence, signs/symptoms, and treatment of anaphylaxis are included in this review article. RESULTS: Although anaphylaxis is a rare event with allergy testing and immunotherapy, it can result in fatal consequences. Clinical manifestations of anaphylaxis are rapid, and the upper and lower airways, skin, conjunctiva, and gastrointestinal and cardiovascular systems are often affected, individually or in combination. Treatment of anaphylaxis in the office begins with proper preparation in advance. The most important drug in the treatment of anaphylaxis is epinephrine, which should be administered early during an anaphylactic reaction. Recognition of the risks factors for anaphylaxis, such as uncontrolled asthma, may be helpful in order to prevent anaphylaxis. CONCLUSION: Fortunately, Anaphylaxis is a rare occurrence in the allergy office if strict attention is paid to proper testing and treatment principles. Maintaining a high level of vigilance and preparedness is important to increase the chances of a favorable outcome should an anaphylactic episode occur.

Determining safe alternatives for multidrug hypersensitive patients with the alternative triple antibiotic-analgesic test.

BACKGROUND: Drug provocation tests (DPTs) need technical equipment, staff and time. There are very few allergy centres performing DPTs in Turkey. Therefore many patients are referred to these centres. One day triple-double antibiotic or non-steroidal anti-inflammatory drug (NSAID) oral DPT for determining safe alternatives is safe, cost-effective and time saving compared to conventional one day one drug oral DPT. Our aim was to investigate the safety of antibiotic-NSAID oral DPT performed on the same day to find safe alternatives in multidrug hypersensitive patients. METHODS: Forty-two patients who had been diagnosed as having both antibiotic and NSAID hypersensitivity were enrolled to the study between 15 November and 15 July 2010. The reactions were urticaria and/or angio-oedema not including laryngeal oedema for all patients. Two antibiotics-one NSAID or two NSAIDs-one antibiotic triple test have been performed on the same day to study patients (n=22), while the control group (n=20) had taken drugs on three separate days. RESULTS: Only two patients had positive reactions during triple test and two patients had adverse reactions; one had gastric pain, one had nausea. Three patients in the control group had positive reactions. There were no significant differences between the two groups in frequency of adverse and allergic drug reactions (p>0.05). Sixty days were spent for the tests of the control group with only 28 days for the study population. CONCLUSION: Triple test performed with antibiotic and NSAID on the same day for determining safe alternatives for multidrug hypersensitive patients reporting non-life-threatening allergic reactions seems to be safe and time-saving.

The safety of codeine in patients with non-steroidal anti-inflammatory drug hypersensitivity: a preliminary study.

BACKGROUND: Drug provocation testing should be performed before safely prescribing an analgesic for patients that are hypersensitive to non-steroidal anti-inflammatory drugs (NSAIDs). Whether or not the direct histamine releasing effect of codeine renders it useful in NSAID-hypersensitive patients is unknown. This study aimed to determine if codeine could be recommended as a safe treatment option for NSAID-hypersensitive patients without the need for oral drug provocation testing. METHODS: The study included NSAID-hypersensitive patients with and without concurrent asthma, rhinitis, and chronic urticaria that presented to the allergy clinic between 1 January 1991 and 31 December 2010. Patient data were collected from the allergy clinic computer database. Patients challenged with codeine were included in the codeine group. The non-codeine group included those patients that were tested with analgesics other than codeine. RESULTS: In total, data for 1071 patients, of whom 301 were in the codeine group, were analysed. The reaction rate to codeine was 7.3% and when compared in pairs, the rate was significantly lower than to meloxicam and nimesulide (odds ratios=0.26-0.31, respectively). The reaction rate to codeine did not differ from that to benzydamine, rofecoxib, and paracetamol. Symptomatic dermographism was associated (p=0.009) with test positivity to any drug. CONCLUSIONS: Although, codeine was among the safest alternative drugs and none of the patients had an anaphylactic reaction to it, thus a challenge with codeine may be considered especially in patients with dermographism. The results of this preliminary study should be confirmed in a prospective study including a control group.

Incidence and impact of false-positive urine pneumococcal antigen testing in hospitalized patients.

OBJECTIVES: Immunochromatographic urine pneumococcal antigen testing (ICT) has become a common diagnostic tool for those presenting with possible invasive pneumococcal disease. The incidence and clinical impact of ICT false-positivity on hospitalized patients has not been assessed outside of specific patient subpopulations. ICT performance needs to be assessed in a real-world clinical setting. This study aims to describe the incidence and clinical impact of ICT false-positivity in a hospital setting over a 19-month period. METHODS: A retrospective cohort study was performed to assess the incidence of false-positive (FP) ICT among hospitalized patients from November 21, 2007 to June 30, 2009. The primary objective was to describe the incidence of FP ICT results. The secondary objective was to describe what clinical impact, if any, could be attributed to FP ICT results. RESULTS: During the study period, 52 positive ICT results were obtained, of which 5 (9.6%) were deemed falsely positive. Interestingly, two of the 5 FP results were from patients who had received 23-valent pneumococcal vaccine (PPV) in the 2 days prior to ICT. The management of all 5 patients was impacted by the FP results through unnecessary antimicrobial treatment and/or deferral of further clinical evaluation. CONCLUSION: Health care providers should be aware of the potential for ICT FP and should order and interpret these tests within an informed clinical framework.

Induced sputum in children: success determinants, safety, and cell profiles.

BACKGROUND: Sputum induction is a noninvasive method for the assessment of airway inflammation. OBJECTIVES: To evaluate the safety of the procedure and the clinical predictors of successful induction, and to analyze the relationship between sputum cell counts and clinical features in asthmatic and nonasthmatic children. METHODS: We reviewed sputum inductions performed in our department between 2006 and 2008 in individuals under 18 years; 34 asthmatic and 24 nonasthmatic children were included. Sputum induction was performed with 4.5% saline for 5-minute periods with salbutamol pretreatment. The most viscid portions were selected for processing. Inductions which were tolerated for less than 4 minutes or which produced a sample volume of less than 1 mL or a sample with a squamous cell percentage of over 80% were considered unsuccessful. RESULTS: Sputum induction was successful in 43 (74%) of the 58 children studied.The total median induction time was 15 minutes (interquartile range, 10-15 minutes). Only 7 individuals (12%) experienced mild symptoms, which were easily reversed with salbutamol inhalation in all cases. The mean (SD) overall PEF variation with induction was -2.5% (7%), with no significant differences between asthmatics and nonasthmatics. Asthmatics had significantly higher total cell counts (P = .007), macrophages (P = .033), and relatively fewer neutrophils (P = .003) than nonasthmatics; metachromatic cells were rare and seen only in asthmatics (P = .026). We found a positive correlation between exhaled nitric oxide and sputum eosinophil count (r = 0.363, P = .017). CONCLUSIONS: Sputum induction is a safe, noninvasive, and feasible procedure that allows the direct assessment of airway inflammation in most children.

Open challenge for the diagnosis of cow's milk protein allergy.

OBJECTIVE: To report the results of open challenge tests performed in children fed with cow's milk-free diet. DESCRIPTION: Cross-sectional study evaluating cow's milk open challenge performed under supervision in a hospital setting during 2.5 hours and ambulatory follow-up for 30 days when no immediate reaction occurred. One hundred and twenty-one patients were included, with ages between 4 and 95 months. Cow's milk open challenge tests were positive in 28 patients (23.1%). A clinical manifestation of cow's milk allergy different from the one presented at diagnosis occurred in 12 (24.9%) patients with positive challenge. Positive challenge was more frequent (p = 0.042) in patients fed with extensively hydrolyzed formulae or amino acid-based formulae (30.3%) when compared to those fed with other exclusion diets (14.5%). CONCLUSION: Open challenge allowed the interruption of exclusion diet in a significant proportion of the patients.

Teste de desencadeamento aberto no diagnóstico de alergia à proteína do leite de vaca / Open challenge for the diagnosis of cow's milk protein allergy

OBJETIVO: Relatar os resultados de testes de desencadeamento aplicados em crianças alimentadas com dieta de exclusão das proteínas do leite de vaca. DESCRIÇÃO: Estudo transversal que avaliou testes de desencadeamento oral aberto, com leite de vaca, realizados sob supervisão em ambiente hospitalar por 2,5 horas e ambulatoriamente por 30 dias quando não ocorreu reação imediata. Foram incluídos 121 pacientes, com idades entre 4 e 95 meses. O teste de desencadeamento com leite de vaca foi positivo em 28 (23,1 por cento) pacientes. Manifestação clínica de alergia ao leite de vaca diferente da apresentada por ocasião da suspeita diagnóstica ocorreu em 12 (42,9 por cento) pacientes com desencadeamento positivo. O desencadeamento positivo foi mais frequente (p = 0,042) nos pacientes alimentados com fórmulas extensamente hidrolisadas ou de aminoácidos (30,3 por cento) quando comparados com os alimentados com outras dietas de exclusão (14,5 por cento). CONCLUSÃO: O teste de desencadeamento permitiu que fosse suspensa a dieta de exclusão de grande parte dos pacientes.

OBJECTIVES: To report the results of open challenge tests performed in children fed with cow's milk-free diet. DESCRIPTIONS: Cross-sectional study evaluating cow's milk open challenge performed under supervision in a hospital setting during 2.5 hours and ambulatory follow-up for 30 days when no immediate reaction occurred. One hundred and twenty-one patients were included, with ages between 4 and 95 months. Cow's milk open challenge tests were positive in 28 patients (23.1 percent). A clinical manifestation of cow's milk allergy different from the one presented at diagnosis occurred in 12 (24.9 percent) patients with positive challenge. Positive challenge was more frequent (p = 0.042) in patients fed with extensively hydrolyzed formulae or amino acid-based formulae (30.3 percent) when compared to those fed with other exclusion diets (14.5 percent). CONCLUSION: Open challenge allowed the interruption of exclusion diet in a significant proportion of the patients.