Paloma Campo

Local allergic rhinitis: Concept, pathophysiology, and management

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy characterized by local production of specific IgE (sIgE) antibodies, a T(H)2 pattern of mucosal cell infiltration during natural exposure to aeroallergens, and a positive nasal allergen provocation test response with release of inflammatory mediators (tryptase and eosinophil cationic protein). Although the prevalence remains to be established, a number of patients previously given a diagnosis of nonallergic rhinitis or idiopathic rhinitis are now being classified as having LAR. Culprit allergens responsible include house dust mite, grass and olive pollens, and many others. For the diagnosis of LAR, neither skin prick testing nor determination of the presence of serum sIgE antibodies is useful, and a nasal allergen provocation test is needed to identify the culprit allergen or allergens. In a certain proportion of cases, local sIgE can be detected, and conjunctivitis, asthma, or both can be associated. Whether patients with LAR will have systemic atopy in the future is a matter of debate. Further studies are needed for examine the prevalence of this phenomenon in different areas, to improve the diagnostic methods to better identify these patients, and to develop therapeutic approaches, including the use of immunotherapy.

Characteristics of subjects experiencing hypersensitivity to non-steroidal anti-inflammatory drugs: patterns of response

Background Non‐steroidal anti‐inflammatory drugs (NSAIDs) are one of the most frequently involved groups of medicines in hypersensitivity drug reactions. Two mechanisms can induce the reaction: immunological (sensitization) due to a specific IgE or T cell response and pharmacological (cyclooxygenase inhibition). The contribution of each of these mechanisms to the reactions is not well known.

Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response

Background:  Patients with idiopathic rhinitis (IR) are considered to be nonallergic because they have a negative skin prick test (SPT) and allergen specific‐IgE in serum. The concept of localized mucosal allergy in the absence of atopy has recently been proposed. The immunological mechanisms involved in seasonal IR have not been sufficiently studied. We examined nasal mucosa inflammation, the presence of nasal specific‐IgE and the response to nasal allergen provocation test (NAPT) in patients with seasonal IR who presented symptoms only in spring.

House dust (1-3)-β-D-glucan and wheezing in infants

Background:  (1–3)‐β‐d‐glucan is a fungal cell wall component, suspected to cause respiratory symptoms in adults. However, very little is known on the possible health effects of (1–3)‐β‐d‐glucan during infancy. We examined the association between (1–3)‐β‐d‐glucan exposure and the prevalence of allergen sensitization and wheezing during the first year of life in a birth cohort of 574 infants born to atopic parents. Endotoxin exposure was included as a possible confounder.

Prevalence and clinical relevance of local allergic rhinitis

Evidence demonstrates the existence of local allergic rhinitis (LAR) in nonatopic patients, although its prevalence in the rhinitis population remains unknown. The aim, therefore, of this study was to evaluate the prevalence, clinical characteristics, and severity of LAR in a Spanish rhinitis population, compared with patients having classical allergic rhinitis (AR) with systemic atopy or nonallergic rhinitis (NAR).

Nasal inflammatory mediators and specific IgE production after nasal challenge with grass pollen in local allergic rhinitis

BACKGROUND Evidence exists of a new form of local allergic rhinitis (LAR) with local production of specific IgE (sIgE) and a positive response to nasal allergen provocation test (NAPT) in patients previously diagnosed with idiopathic rhinitis. However, the immunologic mechanisms involved are still poorly understood. OBJECTIVE We explored the involvement of nasal sIgE, eosinophil, and mast cell activation in the response to NAPT with grass pollen (NAPT-grass) in a group of patients already classified with LAR. METHODS Out-of-spring NAPT-grass was performed in 30 patients with LAR and 30 healthy controls. Nasal symptoms, acoustic rhinometry, and nasal lavage were performed at baseline and 15 minutes and 1, 6, and 24 hours post-NAPT. Tryptase, eosinophilic cationic protein (ECP), and total and sIgE to grass pollen were measured in nasal lavage by immunoassays. RESULTS NAPT-grass was positive in all patients with LAR. We detected significant increases of tryptase and ECP in 40% and 43%, respectively, at 15 minutes and 1, 6, and 24 hours post-NAPT compared with baseline (P < .05). sIgE was increased in 30%, with significant increases at 1 and 6 hours (P < .05) and 24 hours (P = .002) post-NAPT. The maximum release of tryptase was detected 15 minutes after NAPT, whereas the maximum release of ECP and sIgE was detected 24 hours after challenge. NAPT-grass was negative in all healthy controls, with no increase in tryptase, ECP, total IgE, or sIgE. CONCLUSION These results demonstrate that patients with LAR had local production of sIgE and mast cell/eosinophil activation induced by nasal exposure to grass pollen.

Evolution of patients with nonallergic rhinitis supports conversion to allergic rhinitis.

BACKGROUND Nonallergic rhinitis (NAR) affects a significant number of patients in clinical practice. However, the different entities involved within NAR require further study. Once allergy has been ruled out, most of these patients are not usually followed up in allergy clinics, despite the persistence of rhinitis symptoms. Thus few data are available concerning the natural evolution of these patients. OBJECTIVE We sought to re-evaluate over time the severity, accompanying disorders, and possible allergen sensitizations in subjects with NAR. METHODS A representative sample of 180 patients given diagnoses of NAR during 2000-2004 was re-evaluated in 2007 by using sociodemographic and clinical questionnaires, spirometry, skin prick testing, and measurement of specific IgE to common aeroallergens. RESULTS Patients with NAR generally experienced worsening disease (52%), with an increase in the persistence (12%) and severity of nasal symptoms (9%) and new comorbidities (24%) over time. The most frequent comorbidities at the re-evaluation were asthma (increasing from 32% to 55%) and conjunctivitis (from 28% to 43%), followed by chronic rhinosinusitis. Sensitization to aeroallergens not present at the initial evolution was detected by means of skin prick testing, serum specific IgE measurement, or both in 24% of the patients. CONCLUSIONS Persistent moderate-to-severe rhinitis associated with asthma, conjunctivitis, or both and sensitization to aeroallergens are likely to appear at a later date in adults initially given diagnoses of NAR. A periodic re-evaluation of these patients might therefore be necessary.

Immediate and dual response to nasal challenge with Dermatophagoides pteronyssinus in local allergic rhinitis

Background Local allergic rhinitis (LAR) is characterized by in situ production of specific IgE (sIgE) antibodies and a positive response to a nasal allergen provocation test (NAPT) in the absence of atopy.

Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL-13 genes

BACKGROUND Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined. OBJECTIVE To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are associated with DA. METHODS Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes. RESULTS No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01). CONCLUSIONS Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.

Local allergic rhinitis: Allergen tolerance and immunologic changes after preseasonal immunotherapy with grass pollen

clinical population classified on the basis of ICD-9 codes alone. In particular, the ORMDL3/GSDML locus associations, which have been replicated in many GWA studies composed of carefully recruited subjects, can also be observed in a white population identified via extracted ICD-9 codes from EMRs. Despite the current small sample size of black subjects, it is evident from our data, and consistent with reported GWA studies, that the allelic frequency distribution among black subjects can be markedly different than that among white subjects at some of the loci that are most prominently reported in GWA studies. Thus, continuing to pursue asthma GWA studies in black subjects, as well as subjects of diverse ethnic backgrounds, will likely yield important insights into the genetics of asthma. Despite the disadvantages related to a more incomplete characterization of disease and environmental variables than that provided by traditional epidemiologic and clinical trial populations, iCAP and other general clinical populations are likely to provide a faster and more cost-effective means to conduct genomic studies of asthma. The insights gained through studies of these general clinical populations will complement those of traditional ones. Blanca E. Himes, PhD Barbara Klanderman, PhD Isaac S. Kohane, MD, PhD Scott T. Weiss, MD, MS