Studies of avoidance of exposure to group 1 allergens of the Dermatophagoides group (Der p 1) have not yielded consistent improvements in adult asthma through avoidance. We explored whether the use of pillow and bed covers and allergen-avoidance counseling resulted in Der 1-level reduction, as measured by enzyme-linked immunosorbent assay, and thus improved asthma symptoms in adult patients.
Twenty-five adult patients with moderate or severe atopic asthma were randomized into intervention and control groups. Intervention patients slept on pillows and mattresses or futons encased in microfine-fiber covers and were counseled in allergen avoidance through bedroom cleaning. Control patients received neither special covers nor counseling. In the period August to October in 2009 (pre-intervention) and 2010 (post-intervention), dust samples were collected in open Petri dishes placed in bedrooms for 2 weeks and by rapid lifting of dust from bedding and skin using adhesive tape on the morning of 1 day of Petri dish placement. We examined the associations between changes in Der 1 level (as measured by enzyme-linked immunosorbent assay) and clinical symptom score, minimum % peak expiratory flow, and fraction of exhaled nitric oxide.
Der 1 allergen levels on the mattress/futon covers and near the floor of the bedrooms of intervention patients, but not controls, were lower in 2010 than in 2009. From 2009 to 2010, asthma symptom scores decreased significantly, and minimum % peak expiratory flow increased significantly, in intervention patients. The fall in Der p 1 concentration was correlated with a reduction in the fraction of exhaled nitric oxide.
Minimization of Der 1 allergen exposure by encasing pillows and mattresses or futons and receiving counseling on avoiding exposure to indoor allergens improved asthma control in adult patients.
Adult intervention; Allergen; Atopic asthma; Bed cover; Dermatophagoides; Group 1 mite antigen
In patients with asthma, medication adherence is a voluntary behavior that can be affected by numerous factors. Depression is an important co-morbidity in adolescents with asthma that may significantly impact their controller medication adherence and other asthma-related outcomes. The modifying effect of depressive symptoms on an asthma intervention’s ability to improve asthma controller medication adherence among urban adolescents with asthma has not yet been reported.
To assess self-reported symptoms of depression as an effect modifier of the relationship between randomization group and controller medication adherence at 6-month follow-up.
These analyses use data from a randomized controlled trial (RCT) conducted in Detroit high schools to evaluate a tailored asthma management program. The intervention included referrals to school or community resources for students reporting symptoms of depression and other issues. “Elevated depressive symptoms” was defined as a positive answer to ≥ 5 of 7 questions from a validated tool included on the baseline questionnaire. Self-reported adherence to controller medication was collected at intervention onset (session 1) and at 6-month follow up. Analyses were restricted to students with report of a controller medication at baseline. Logistic regression was used to assess elevated depressive symptoms as an effect modifier of the relationship between randomization group and 6-month adherence.
Of the 422 students enrolled in the RCT, a controller medication was reported at intervention onset by n = 123 adolescents (29%). Analyzing this group, we observed an interaction between elevated depressive symptoms and adherence (p = 0.073). Stratified analysis showed better adherence in treatment group adolescents meeting criteria for elevated depressive symptoms at baseline as compared to the control group (adjusted Odds Ratio [aOR] = 9.50; p = 0.024). For adolescents without elevated depressive symptoms at baseline, differences in adherence by group assignment did not reach statistical significance (aOR 1.40, p = 0.49).
In this sample of students reporting controller medications at baseline, report of elevated depressive symptoms at baseline and randomization to the intervention group was associated with significantly better adherence at 6-month follow up when compared to that of a control group. Larger studies are needed to evaluate the impact of depression on the relationship between adherence and asthma intervention effectiveness.
Asthma; Depression; Medication adherence; Randomized controlled trial; Self-management; Adolescents; Urban
Airway remodeling is not specifically targeted by current asthma medications, partly owing to the lack of understanding of remodeling mechanisms, altogether posing great challenges in asthma treatment. Increased airway smooth muscle (ASM) mass due to hyperplasia/hypertrophy contributes significantly to overall airway remodeling and correlates with decline in lung function. Recent evidence suggests that IgE sensitization can enhance the survival and mediator release in inflammatory cells. Human ASM (HASM) cells express both low affinity (FcεRII/CD23) and high affinity IgE Fc receptors (FcεRI), and IgE can modulate the contractile and synthetic function of HASM cells. IgE was recently shown to induce HASM cell proliferation but the detailed mechanisms remain unknown. We report here that IgE sensitization induces HASM cell proliferation, as measured by 3H-thymidine, EdU incorporation, and manual cell counting. As an upstream signature component of FcεRI signaling, inhibition of spleen tyrosine kinase (Syk) abrogated the IgE-induced HASM proliferation. Further analysis of IgE-induced signaling depicted an IgE-mediated activation of Erk 1/2, p38, JNK MAPK, and Akt kinases. Lastly, lentiviral-shRNA-mediated STAT3 silencing completely abolished the IgE-mediated HASM cell proliferation. Collectively, our data provide mechanisms of a novel function of IgE which may contribute, at least in part, to airway remodeling observed in allergic asthma by directly inducing HASM cell proliferation.
Human; Airway remodeling; EdU incorporation; Airway smooth muscle; Syk; MAPK; STAT3
Basophils are important effectors cells in allergic rhinitis (AR) since they are involved in immunoglobulin (Ig) E – mediated inflammation and in the release of pro-inflammatory mediators. Specific subcutaneous immunotherapy (SCIT) provides clear immunologic modulation in some immune cells, however its systemic effects on basophils are not well known.
Peripheral blood (PB) samples from 43 patients with allergic rhinitis mono-sensitized to Dermatophagoides pteronyssinus (Dpt) [33 of them under SCIT with allergoid Dpt extract, in maintenance dose (SCIT), with evaluation just before SCIT injection (SCIT-T0) and 4 hours later (SCIT-T4) and the other 10 Dpt allergic patients never having, in the past, undergone specific immunotherapy treatment (NSIT)], and 15 healthy age- and gender-matched controls (HG), were analyzed. For each sample, the total (t-IgE) and specific IgE (s-IgE) was performed, as well as, the relative frequency and absolute number of PB basophils and receptor-bound IgE and IgG expression were evaluated by flow cytometry and the Histamine N-methyltransferase (HNMT) and tryptase α/β1 (TPSAB1) gene expression was assessed by real-time PCR.
Higher levels of receptor-bound IgE were observed in SCIT patients, which are correlated with the levels of serum t-IgE and s-IgE, whereas no significant differences were observed for receptor-bound IgG. Regarding HNMT mRNA expression, significantly lower expression levels were detected in AR patients compared to HG, independently of type of therapy. Moreover a negative correlation was found between HNMT gene expression and time under SCIT. Conversely, tryptase gene expression was significantly up-regulated in NSIT when compared to HG; however in SCIT patients, tryptase gene expression was significantly decreased than in NSIT patients. No differences were found for any parameter between SCIT-T0 and SCIT-T4 with exception of a transient increased expression of tryptase in SCIT-T4.
PB basophils from patients with AR show altered functional features, which seems to be influenced by SCIT, suggesting that these cells could be useful to clarify the SCIT triggered mechanisms at a systemic level.
Allergic rhinitis; Dermatophagoides pteronyssinus; Basophils; Histamine N-methyltransferase; Tryptase; Specific subcutaneous immunotherapy
There are few treatment options for patients with severe atopic asthma. Antagonism of IgE is an effective strategy. We investigated, by utilizing serum samples from a clinical trial of Rituximab in patients with Idiopathic Thrombocytopenic Purpura, if B cell depletion would decrease serum IgE and therefore be a potential therapeutic option.
In a placebo-controlled randomized clinical trial of Rituximab, an anti-CD20 molecule, there were no significant differences in serum levels of IgE or BAFF levels between the two treatment groups at 3 or 6 months irrespective of the baseline serum IgE levels.
Since Rituximab did not significantly decrease serum IgE levels, this proof of concept study suggests that Rituximab may not be a useful treatment strategy for patients with severe IgE mediated disease.
Anti-CD20; Rituximab; Immunoglobulin E; BAFF; Asthma
Symtomatology of nasal polyps (NP) is relatively non-specific and other nasal conditions that cause nasal may be mistaken for NP. The purpose of this study was to evaluate the accuracy otoscopic (OT) examination in detecting presence of NP by using fiberoptic rhinoscopy (FR) as the gold standard to confirm diagnosis of NP.
Charts from a single allergy clinic were reviewed for any patient having NP diagnosed by FR. Data collected included gender, age, allergy skin test results, and presence of asthma, aspirin allergy, previous nasal surgeries, intranasal corticosteroid use and leukotriene receptor antagonist use.
The OT examination had 44% sensitivity. In this study, more than half (56%) of patients with NP would have had their NP missed if FR had not been performed in addition to the OT examination.
The standard physical examination procedure is often not sufficient to confirm a diagnosis of NP. FR should be considered in the investigation of patients with rhinitis symptoms.
Atopic asthma is characterized by intermittent exacerbations triggered by exposure to allergen. Exacerbations are characterized by an acute inflammatory reaction in the airways, with recruitment of both innate and adaptive immune cells. These cell populations as well as soluble factors are critical for initiating and controlling the inflammatory processes in allergic asthma. Detailed data on the numbers and types of cells recruited following allergen challenge is lacking. In this paper we present an extensive phenotypic analysis of the inflammatory cell infiltrate present in the bronchoalveolar lavage (BAL) fluid following bronchoscopically directed allergen challenge in mild atopic asthmatics.
A re-analysis of pooled data obtained prior to intervention in our randomized, placebo controlled, double blinded study (costimulation inhibition in asthma trial [CIA]) was performed. Twenty-four subjects underwent bronchoscopically directed segmental allergen challenge followed by BAL collection 48 hours later. The BAL fluid was analyzed by multi-color flow cytometry for immune cell populations and multi-plex ELISA for cytokine detection.
Allergen instillation induced pro-inflammatory cytokines (IL-6) and immune modulating cytokines (IL-2, IFN-γ, and IL-10) along with an increase in lymphocytes and suppressor cells (Tregs and MDSC). Interestingly, membrane expression of CD30 was identified on lymphocytes, especially Tregs, but not eosinophils. Soluble CD30 was also detected in the BAL fluid after allergen challenge in adult atopic asthmatics.
After segmental allergen challenge of adult atopic asthmatics, cell types associated with a pro-inflammatory as well as an anti-inflammatory response are detected within the BAL fluid of the lung.
T lymphocyte; CD30 expression; Segmental allergen challenge; Asthma
We describe the first case of a patient with factitious disorder who closely simulated a primary immune deficiency disorder – Common Variable Immune Deficiency (CVID), by surreptitiously ingesting non-steroidal anti-inflammatory agents.
He was treated with several expensive and potentially dangerous drugs before the diagnosis was established through collateral information. In retrospect he did not meet the proposed new criteria for CVID. These criteria may prove useful in distinguishing cases of CVID from secondary hypogammaglobulinemia.
It is imperative clinicians recognise patients with factitious disorder at the earliest opportunity to prevent iatrogenic morbidity and mortality.
Factitious disorder; NSAID; CVID; Hypogammaglobulinemia factitia; Munchausen syndrome
The eliciting dose (ED) for a peanut allergic reaction in 5% of the peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was derived from oral food challenges (OFC) that use graded, incremental doses administered at fixed time intervals. Individual patients’ threshold doses were used to generate population dose-distribution curves using probability distributions from which the ED05 was then determined. It is important to clinically validate that this dose is predictive of the allergenic response in a further unselected group of peanut-allergic individuals.
This is a multi-centre study involving three national level referral and teaching centres. (Cork University Hospital, Ireland, Royal Children’s Hospital Melbourne, Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in process and will continue to run until all centres have recruited 125 participates in each respective centre.
A total of 375 participants, aged 1–18 years will be recruited during routine Allergy appointments in the centres. The aim is to assess the precision of the predicted ED05 using a single dose (6 mg peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered prior to OFC and 1 month after challenge to assess the impact of a single dose OFC on FAQL. Serological and cell based in vitro studies will be performed.
The validation of the ED05 threshold for allergic reactions in peanut allergic subjects has potential value for public health measures. The single dose OFC, based upon the statistical dose-distribution analysis of past challenge trials, promises an efficient approach to identify the most highly sensitive patients within any given food-allergic population.
Eliciting dose (ED); Food Allergy related Quality of Life Questionnaires-(FAQLQ); Single dose; Peanut thresholds; Oral Food Challenges (OFC); Voluntary Incidental Trace Allergen Labelling (VITAL); Peanut Allergen Threshold Study (PATS)
Referring to individuals with reactivity to honey bee and Vespula venom in diagnostic tests, the umbrella terms “double sensitization” or “double positivity” cover patients with true clinical double allergy and those allergic to a single venom with asymptomatic sensitization to the other. There is no international consensus on whether immunotherapy regimens should generally include both venoms in double sensitized patients.
We investigated the long-term outcome of single venom-based immunotherapy with regard to potential risk factors for treatment failure and specifically compared the risk of relapse in mono sensitized and double sensitized patients.
Re-sting data were obtained from 635 patients who had completed at least 3 years of immunotherapy between 1988 and 2008. The adequate venom for immunotherapy was selected using an algorithm based on clinical details and the results of diagnostic tests.
Of 635 patients, 351 (55.3%) were double sensitized to both venoms. The overall re-exposure rate to Hymenoptera stings during and after immunotherapy was 62.4%; the relapse rate was 7.1% (6.0% in mono sensitized, 7.8% in double sensitized patients). Recurring anaphylaxis was statistically less severe than the index sting reaction (P = 0.004). Double sensitization was not significantly related to relapsing anaphylaxis (P = 0.56), but there was a tendency towards an increased risk of relapse in a subgroup of patients with equal reactivity to both venoms in diagnostic tests (P = 0.15).
Single venom-based immunotherapy over 3 to 5 years effectively and long-lastingly protects the vast majority of both mono sensitized and double sensitized Hymenoptera venom allergic patients. Double venom immunotherapy is indicated in clinically double allergic patients reporting systemic reactions to stings of both Hymenoptera and in those with equal reactivity to both venoms in diagnostic tests who have not reliably identified the culprit stinging insect.
Anaphylaxis; Double sensitization; Field sting; Honey bee; Hymenoptera venom; Immunotherapy; Relapse; Risk factor; Treatment failure; Vespula
Since barrier protection measures to avoid contact with allergens are being increasingly developed, we assessed the clinical efficacy and tolerability of a topical nasal microemulsion made of glycerol esters in patients with allergic rhinitis.
Randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial in which adult patients with allergic rhinitis or rhinoconjunctivitis due to sensitization to birch, grass or olive tree pollens received treatment with topical microemulsion or placebo during the pollen seasons. Efficacy variables included scores in the mini-RQLQ questionnaire, number and severity of nasal, ocular and lung signs and symptoms, need for symptomatic medications and patients’ satisfaction with treatment. Adverse events were also recorded.
Demographic characteristics were homogeneous between groups and mini-RQLQ scores did not differ significantly at baseline (visit 1). From symptoms recorded in the diary cards, the ME group showed statistically significant better scores for nasal congestion (0.72 vs. 1.01; p = 0.017) and mean total nasal symptoms (0.7 vs. 0.9; p = 0.045). At visit 2 (pollen season), lower values were observed in the mini-RQLQ in the ME group, although there were no statistically significant differences between groups in both full analysis set (FAS) and patients completing treatment (PPS) populations. The results obtained in the nasal symptoms domain of the mini-RQLQ at visit 2 showed the highest difference (−0.43; 95% CI: -0.88 to 0.02) for the ME group in the FAS population. The topical microemulsion was safe and well tolerated and no major discomforts were observed. Satisfaction rating with the treatment was similar between the groups.
The topical application of the microemulsion is a feasible and safe therapy in the prevention of allergic symptoms, particularly nasal congestion.
ClinicalTrials.gov Identifier: NCT01478425
Allergic rhinitis; Rhinoconjunctivitis; Allergen avoidance; Barrier measures; Corticosteroids use; Nasal symptoms; Natural pollen exposure; Quality of life; Efficacy; Safety
There is a lack of objective measures of the clinical efficacy of allergen immunotherapy which relies on patients’ perception about the effect of this treatment. We studied whether the fraction of exhaled nitric oxide is affected by multiple allergen immunotherapy in polysensitized adult subjects with allergic rhinitis. We also looked for associations between exhaled nitric oxide and subjects’ demographics, symptom scores, and pulmonary function tests.
Twenty adult, polysensitized subjects with seasonal and perennial allergic rhinitis who chose to undergo allergen immunotherapy were enrolled. They were evaluated at baseline, and 4, 8, 12, 24, and 52 weeks later. Exhaled nitric oxide was reported as the mean of triplicate determinations.
Our results indicate that multiple allergen immunotherapy did not affect exhaled nitric oxide levels and such levels did not correlate with subjects’ demographics and pulmonary function tests. However, exhaled nitric oxide was associated with rhinoconjuctivitis and asthma symptom scores at the end of the study.
In polysensitized adult subjects with allergic rhinitis, exhaled nitric oxide levels are unaffected by multiple allergen immunotherapy.
Allergen immunotherapy; Nitric oxide; Allergic rhinitis
Systemic corticosteroids play an integral role in the management of many inflammatory and immunologic conditions, but these agents are also associated with serious risks. Osteoporosis, adrenal suppression, hyperglycemia, dyslipidemia, cardiovascular disease, Cushing’s syndrome, psychiatric disturbances and immunosuppression are among the more serious side effects noted with systemic corticosteroid therapy, particularly when used at high doses for prolonged periods. This comprehensive article reviews these adverse events and provides practical recommendations for their prevention and management based on both current literature and the clinical experience of the authors.
Adverse events; Adrenal suppression; Corticosteroids; Cushing’s syndrome; Hyperglycemia; Glaucoma; Glucocorticoids; Glucocorticoid-induced osteoporosis; Side effects; Systemic
Hereditary angioedema (HAE) is a rare, debilitating, and potentially life-threatening disease characterized by recurrent edema attacks. Important advances in HAE treatment have been made, including the development of new therapies for treating or preventing attacks. Nevertheless, the disease is still frequently misdiagnosed and inappropriately treated, potentially exposing patients with laryngeal attacks to the risk of asphyxiation.
The Icatibant Outcome Survey (IOS) is an international, observational study that documents the clinical outcome of HAE patients eligible for treatment with icatibant. Patient ages at first symptoms and at diagnosis were recorded at enrolment, and the delay between first symptoms and diagnosis was calculated.
The median [range] diagnostic delay in HAE type I and II patients across eight countries was 8.5 years [0–62.0]. The median delay in diagnosis was longer for HAE type II versus type I (21 versus 8 years, respectively), although this did not quite reach statistical significance.
Although it can be difficult to differentiate HAE symptoms from those of more common angioedema sub-types (e.g. idiopathic or acquired angioedema), our results show that HAE type I and II patients have an unacceptable delay in diagnosis, even those with a family history of the disease. Raising physician awareness of this disabling and potentially fatal disease may lead to a more accurate diagnosis and timely treatment.
Bradykinin; C1-inhibitor; Diagnosis; Hereditary angioedema; Icatibant
Oral corticosteroid prescriptions are often used in clinical studies as an indicator of asthma exacerbations. However, there is rarely the ability to link a prescription to its associated diagnosis. The objective of this study was to characterize patterns of oral corticosteroid prescription orders for asthma patients using an electronic health record database, which links each prescription order to the diagnosis assigned at the time the order was placed.
This was a retrospective cohort study of the electronic health records of asthma patients enrolled in the Geisinger Health System from January 1, 2001 to August 23, 2010. Eligible patients were 12–85 years old, had a primary care physician in the Geisinger Health System, and had asthma. Each oral corticosteroid order was classified as being prescribed for an asthma-related or non-asthma-related condition based on the associated diagnosis. Asthma-related oral corticosteroid use was classified as either chronic or acute. In patient-level analyses, we determined the number of asthma patients with asthma-related and non-asthma-related prescription orders and the number of patients with acute versus chronic use. Prescription-level analyses ascertained the percentages of oral corticosteroid prescription orders that were for asthma-related and non-asthma-related conditions.
Among the 21,199 asthma patients identified in the electronic health record database, 15,017 (70.8%) had an oral corticosteroid prescription order. Many patients (N = 6,827; 45.5%) had prescription orders for both asthma-related and non-asthma-related conditions, but some had prescription orders exclusively for asthma-related (N = 3,450; 23.0%) or non-asthma-related conditions (N = 4,740; 31.6%). Among the patients receiving a prescription order, most (87.5%) could be classified as acute users. A total of 60,355 oral corticosteroid prescription orders were placed for the asthma patients in this study—31,397 (52.0%) for non-asthma-related conditions, 24,487 (40.6%) for asthma-related conditions, and 4,471 (7.4%) for both asthma-related and non-asthma-related conditions.
Oral corticosteroid prescriptions for asthma patients are frequently ordered for conditions unrelated to asthma. A prescription for oral corticosteroids may be an unreliable marker of asthma exacerbations in retrospective studies utilizing administrative claims data. Investigators should consider co-morbid conditions for which oral corticosteroid use may also be indicated and/or different criteria for assessing oral corticosteroid use for asthma.
Oral corticosteroids; Asthma; Anti-asthmatic agents; Retrospective studies; Therapeutic use; Managed care programs; Cross-sectional studies
Atopic dermatitis (AD) is a condition frequently encountered in medical practices across the country. Arming ourselves with appropriate and safe treatment modalities to provide relief for this chronic and relapsing inflammatory condition is of utmost importance to our patients and their families. Utilizing topical calcineurin inhibitors (TCIs) for the treatment of AD not responsive to high-potency corticosteroids, or low-potency corticosteroids and localized to the face, eyelids, and skin folds of patients >2 years, is reasonable to include in common practice. Despite the FDA’s Black Box warning, to date no evidence has been published linking the TCIs to an increased incidence of malignancy in either children or adults that establishes causation. The Canadian Society of Allergy and Clinical Immunology (CSACI) therefore recognizes that the benefits of TCIs should be carefully weighed with the theoretical risks in advising patients, and acknowledges that long-term studies remain in progress. The safety and efficacy of topical tacrolimus and pimecrolimus should therefore be considered when treating children and adults with AD in Canadian allergy and immunology practices.
Atopic dermatitis; Topical corticosteroids; Therapy; Tacrolimus; Pimecrolimus; Lymphoma; Drug safety
The first documented confirmed case of an imported fire ant causing anaphylaxis in Canada is herein reported. In a patient with anaphylaxis to ants a physician in Canada should be aware that an allergic reaction to fire ant is a possibility.
A T helper cell (TH) 17-biased response has been observed in patients with allergic asthma, particularly in those with neutrophil accumulation in the lung. Therefore, we sought to test the hypothesis that neutrophils might be an important source of interleukin (IL)-17 in allergic asthma.
Whole peripheral blood cells from non-asthmatic control subjects (n = 17) and patients with mild asthma (n = 7), moderate but persistent asthma (n = 4), or acute asthma (n = 6) were analyzed for IL-17A expression in CD177+ neutrophils. IL-17A expression was also analyzed in CD3+CD4+ and CD3+CD8+ lymphocyte populations. Asthmatic patients were classified as allergic to fungi, indoor allergens, or other allergens (e.g., pollen) based on a positive intradermal allergy test reaction.
The percentage of CD177+ neutrophils in whole blood of asthmatic patients was higher than in healthy controls and highest in the moderate asthma group. Furthermore, the percentage of CD177+IL-17+ neutrophils was elevated in patients with mild asthma, whereas the CD4+ IL-17+ lymphocyte population was higher in asthmatic patients and highest in those with moderate but persistent asthma. We also found that the four patients that were allergic to fungi had the highest percentage of CD177+IL17+ neutrophils and CD8+IL17+ lymphocytes.
IL17+CD177+ Neutrophils increase in allergic asthma patients especially when allergic to fungi. This cell population, through release of IL-17, might be contributing during the initial phase asthmatic disease and/or during disease progression but its role has not yet been established.
Neutrophils; IL-17; Allergic asthma; Blood
Diagnostic testing to antibiotics other than to penicillin has not been widely available, making the diagnosis of antibiotic allergy difficult and often erroneous. There is often reluctance in performing challenges to antibiotics when standardized testing is lacking. However, while the immunogenic determinants are not known for most antibiotics, a skin reaction at a non-irritating concentration (NIC) may mean that antibodies to the native form are present in the circulation. While the NIC’s for many non penicillin antibiotics have been determined in adults, the use of these concentrations for skin testing pediatric subjects prior to provocative challenge has not been done. Our objective was to determine if we could successfully uncover the true nature of antibiotic allergy in children using these concentrations for testing.
Children were included between 2003–2009 upon being referred to the Drug and Adverse Reaction/Toxicology (DART) clinic of the Hospital for Sick Children in Toronto, Ontario Canada. The referral needed to demonstrate that clinical care was being compromised by the limitation in antibiotic options or there was a significant medical condition for which the label of antibiotic allergy may prove detrimental. Patients were not seen if there was a suggestion of serum like sickness, Stevens Johnson Syndrome or Toxic Epidermal Necrolysis. Patients were excluded from testing if there was objective evidence of anaphylaxis. All other patients were consented to receive testing and/or challenges. A retrospective chart review was then performed of the results.
We were able to exclude an antibiotic allergy in the majority of our patients who had a negative intradermal test result and were then challenged (>90%). Only one patient was challenged with a positive intradermal test to Cotrimoxazole because of a questionable history and this patient failed the provocative challenge. While we did not challenge more patients with positive testing, we did note that 10/11 (91%) patients with positive intradermal testing had some aspect of a Type 1 reaction in their history.
Through testing with NIC’s of various antibiotics in children and providing provocative challenges based on negative skin testing results, we were able to advance the medical care of the majority of our patients by increasing their antibiotic options in order to successfully treat future infections. While challenging patients with positive testing was not deemed ethically appropriate at this stage of our study, it would be a useful future step to reaching statistical validity of testing to these antibiotics.
Antibiotic allergy; Drug testing; Skin testing; Provocative challenge
Allergen-specific immunotherapy has been demonstrated to have potential for the treatment of allergic diseases. Transgenic animals are currently the best available bioreactors to produce recombinant proteins, which can be secreted in milk. It has not been clearly demonstrated whether milk from transgenic animals expressing recombinant allergens has immunomodulatory effects on allergic asthma.
We aimed to determine whether the oral administration of milk containing a mite allergen can down-regulate allergen-specific airway inflammation. Transgenic CD-1 mice that express a recombinant group 2 allergen from Dermatophagoides pteronyssinus (Dp2) in their milk were generated using an embryonic gene-microinjection technique. Mouse pups were fed transgenic Dp2-containing milk or wild-type milk. Subsequently, these mice were sensitized and challenged with Dp2 to induce allergic airway inflammation.
Upon sensitization and challenge, mice fed transgenic Dp2 milk had decreased T-helper 2 (Th2) and increased T-helper 1 (Th1) responses in the airway compared with mice fed wild-type milk. Moreover, pre-treatment with transgenic Dp2 milk attenuated airway inflammation and decreased airway hyper-responsiveness.
This study provides new evidence that oral administration of transgenic milk containing the Dp2 allergen down-regulated and moderately protected against allergic airway inflammation. Milk from transgenic animals expressing allergens may have potential use in the prevention of allergic asthma.
Transgenic mice; Allergen; Asthma; Immunotherapy; Group 2 allergen of Dermatophagoides pteronyssinus; Tolerance
Studies on time trends of allergic sensitization among adults are rare. The aim of the study was to compare the prevalence of allergic sensitization to common airborne allergens among adults 15 years apart and to identify risk factors for allergic sensitization.
Clinical examinations including skin prick test (SPT) and structured interviews were performed in two random population samples in 1994 and 2009. Furthermore, specific IgE was analyzed in 2009. SPT data were available for 483 subjects in 1994 and for 463 subjects in 2009 in ages 20–60 years. Specific IgE was analyzed in 692 subjects in ages 20–79 years.
Sensitization to cat (16% to 26%, p < 0.001), dog (13% to 25%, p < 0.001), birch (13% to 18%, p = 0.031) and timothy (12% to 21%, p < 0.001), based on SPT, increased significantly from 1994 to 2009. Sensitization to any positive SPT increased from 35% to 39%, p = 0.13.The proportion of having ≥3 positive SPT reactions increased from 40% to 56%, p = 0.002. The sensitization pattern yielded similar results based on specific IgE. Risk factors for allergic sensitization were having a family history of allergy (OR 3.1, 95% CI 2.0-4.8 for any positive SPT; OR 2.7, 95% CI 1.8-4.0 for any elevated IgE) and urban living (OR 1.7, 95% CI 1.0-2.7; OR 1.5, 95% CI 1.0-2.4).
The prevalence of allergic sensitization to major airborne allergens as well as multi-sensitization increased significantly between the study years. Young age, a family history of allergy and urban living were significant risk factors for allergic sensitization.
Allergic sensitization; Epidemiology; IgE; Population study; Prevalence; Skin prick test
Atmospheric contamination caused by Asian sand-dust (ASD) storms aggravates asthma in both human adults and children. This study aims to investigate a series of manifestations in allergic airway disease caused by co-exposure to allergens and ASD for 6 weeks and 14 weeks.
CD-1 Mice were instilled intratracheally with 0.1 mg of ASD/mouse four times (6 weeks) or eight times (14 weeks) at 2-week intervals (total dose of 0.4 mg or 0.8 mg/mouse) with or without ovalbumin (OVA). The pathologic changes in the airway, cytological alteration in bronchoalveolar lavage fluid (BALF), and levels of inflammatory cytokines/chemokines in BALF, and OVA-specific IgE and IgG1 antibodies in serum were measured in the treated CD-1 mice.
Four-time co-exposure to OVA and ASD aggravates allergic airway inflammation along with Th2-cytokine IL-13 and eosinophil-relevant cytokine/chemokines IL-5, Eotaxin and MCP-3 in BALF, and fibrous thickening of the subepithelial layer in the airway. On the other hand, eight-time co-exposure attenuates these changes along with a significant increase of TGF-β1 in BALF. Adjuvant effects of ASD toward IgG1 and IgE production in sera were, however, still seen in the eight-time co-exposure.
These results indicate that the immune responses in airways are exacerbated by four-time co-exposure to ASD with OVA, but that there is a shift to suppressive responses in eight-time co-exposure, suggesting that the responses are caused by TGF-β1-related immune tolerance.