Omalizumab: Anti-IgE Therapy in Allergy

Current Allergy and Asthma Reports (Jan 2011)

 Kopp MV 

Omalizumab is a humanized, monoclonal anti-IgE antibody that binds specifically to circulating IgE molecules, thus interrupting the allergic cascade. Omalizumab has been shown to be highly effective in treating children and adults with moderate to severe allergic asthma. Beyond this indication, the mode of action itself suggests that omalizumab is not only an antiasthmatic drug but also a promising therapeutic option for various allergic conditions, including allergic rhinitis, food allergy, urticaria, allergic bronchopulmonary aspergillosis, insect hypersensitivity, and atopic dermatitis. However, data from double-blind, placebo-controlled clinical trials are only available for allergic rhinitis and moderate to severe bronchial asthma. The aim of this review is to discuss the current clinical data as well as possible further indications of omalizumab treatment

Vocal cord dysfunction: what do we know?

European Respiratory Journal 37 (1), 194-200 (Jan 2011)

Kenn K, Balkissoon R 

Vocal cord dysfunction (VCD) is a disorder caused by episodic unintentional paradoxical adduction of the vocal cords, which may induce acute severe dyspnoea attacks not responsive to conventional asthma therapy. The aetiology of VCD is complex and often multifactorial. The essential pathophysiology is that of a hyperfunctional laryngeal reflex to protect the lower airway as a result of any combination of post-nasal drip, gastro-oesophageal reflux, laryngopharyngeal reflux and/or psychological conditions. Laryngoscopic demonstration of the paradoxical motion while wheezing or stridorous is considered the diagnostic gold standard. Speech therapy, including the use of special relaxed-throat breathing patterns is effective for VCD that is purely of the functional nature. Knowledge of the clinical features of VCD and identifying factors that may be contributing to the development of VCD can provide adequate clues to the correct diagnosis and management.

Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults

Journal of Allergy and Clinical Immunology (JACI) 127 (1), 72-80.e2 (Jan 2011)

Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI 

BACKGROUND Immunotherapy for allergic rhinoconjunctivitis (ARC) in North America is generally administered subcutaneously, but alternative formulations might be safer and more convenient. Trials of sublingual formulations in North America are needed to confirm European efficacy and safety data. 

OBJECTIVEWe sought to investigate the efficacy and safety of timothy grass allergy immunotherapy tablet (AIT) treatment in North American subjects with ARC. 

METHODS Four hundred thirty-nine adults with grass pollen-induced ARC with or without asthma were randomized to once-daily 2,800 bioequivalent allergen units of standardized grass AIT (oral lyophilisate, Phleum pratense, 75,000 standardized quality tablet, containing approximately 15 μg of Phl p 5) or placebo approximately 16 weeks before the 2009 grass pollen season (GPS). The primary end point was the average total combined score of the daily symptom score and the daily medication score during the GPS. Rhinoconjunctivitis Quality of Life Questionnaire with standardized activities (RQLQ[S]) scores, Phl p 5-specific IgG4 levels, and IgE-blocking factor levels were additional end points. Adverse events (AEs) were monitored for safety. 

RESULTS Relative to placebo, grass AIT treatment improved total combined scores by 20% (P = .005), daily symptom scores by 18% (P = .02), and RQLQ(S) scores by 17% (P = .02). Daily medication scores were improved by 26% and trended toward significance (P = .08). Phl p 5-specific IgG4 and IgE-blocking factor levels were higher after grass AIT treatment compared with those after placebo at the end of the GPS (P <.001). Grass AIT treatment was safe and well tolerated. The majority of AEs were transient mild local reactions with no investigator-diagnosed grass AIT-related serious AEs or reports of anaphylactic shock/respiratory compromise. In the grass AIT group, 1 subject received epinephrine after experiencing a possible grade 1 systemic reaction (local site reactions, chest discomfort, and rash). 

CONCLUSIONS Timothy grass AIT treatment (cross-reactive with related Pooideae grasses) was demonstrated to be effective, generally safe, and well tolerated in North American adults with grass pollen-induced ARC.

Chronic cough and irritable larynx

Journal of Allergy and Clinical Immunology (JACI) (Dec 2010) 

Bucca CB, Bugiani M, Culla B, Guida G, Heffler E, Mietta S, Moretto A, Rolla G, Brussino L

BACKGROUND: Perennial rhinitis (PR), chronic rhinosinusitis (CRS), or both, asthma, and gastroesophageal reflux disease (GERD) are the most frequent triggers of chronic cough (CC). Extrathoracic airway receptors might be involved in all 3 conditions because asthma is often associated with PR/CRS and gastroesophageal refluxate might reach the upper airway. We previously found that most patients with rhinosinusitis, postnasal drip, and pharyngolaryngitis show laryngeal hyperresponsiveness (LHR; ie, vocal cord adduction on histamine challenge) that is consistent with an irritable larynx. 

OBJECTIVE: We sought to evaluate the role of LHR in patients with CC. 

METHODS: LHR and bronchial hyperresponsiveness (BHR) to histamine were assessed in 372 patients with CC and in 52 asthmatic control subjects without cough (asthma/CC-). In 172 patients the challenge was repeated after treatment for the underlying cause of cough. RESULTS: The primary trigger of CC was PR/CRS in 208 (56%) patients, asthma in 41 (11%) patients (asthma/CC+), GERD in 62 (17%) patients, and unexplained chronic cough (UNEX) in 61 (16%) patients. LHR prevalence was 76% in patients with PR/CRS, 77% in patients with GERD, 66% in patients with UNEX, 93% in asthma/CC+ patients, and 11% in asthma/CC- patients. Upper airway disease was found in most (95%) asthma/CC+ patients and in 6% of asthma/CC- patients. BHR discriminated asthmatic patients and atopy discriminated patients with PR/CRS from patients with GERD and UNEX. Absence of LHR discriminated asthmatic patients without cough. After treatment, LHR resolved in 63% of the patients and improved in 11%, and BHR resolved in 57% and improved in 18%. 

CONCLUSIONS: An irritable larynx is common in patients with CC and indicates upper airway involvement, whether from rhinitis/sinusitis, gastric reflux, or idiopathic sensory neuropathy.

Early exposure to paracetamol or to antibiotics and eczema at school age: Modification by asthma and rhinoconjunctivitis

Pediatric Allergy and Immunology (Apr 2010)

Garcia-Marcos L, González-Díaz C, Garvajal-Urueña I, Pac-Sa MR, Busquets-Monge RM, Suárez-Varela MM, Batlles-Garrido J, Blanco-Quirós A, Varela AL, García-Hernández G, Aguinaga-Ontoso I

The association between early exposure to paracetamol or to antibiotics and eczema is conflicting. This study aims to know whether the early exposure to those drugs is associated with eczema at school age, and whether the strength of the association is modified by the presence of asthma or rhinoconjunctivitis.

Children aged 6-7 (n = 13908) from the International Study of Asthma and Allergies in Childhood in Spain provided data about current asthma, rhinoconjunctivitis and eczema. Parent-reported information was also obtained on paracetamol and antibiotic consumption during the first year of life. Logistic regression analysis with eczema as outcome and including exposure to paracetamol or to antibiotics, together with possible confounders, was carried out in the whole sample of children and in five different strata: no respiratory symptom and any respiratory symptom further subdivided into: asthma with rhinoconjunctivitis, asthma without rhinoconjunctivitis and rhinoconjunctivitis without asthma. In the whole sample, exposure to paracetamol was associated with eczema (aOR 1.56 [1.36-1.80]) as was antibiotic consumption (aOR 1.66 [1.43-1.92]). These associations did not substantially change after additionally adjusting for the other drug. A similar pattern was found among children without respiratory symptoms.
In children with symptoms, adjusting for the other drug modified the association with paracetamol (aOR from 1.32 [1.03-1.71] to 1.09 [0.83-1.43]) but did not change that with antibiotics (aOR from 1.80 [1.38-2.35] to 1.81 [1.37-2.39]). Early exposure to paracetamol or to antibiotics is associated with an increased prevalence of eczema at school age. Asthma and/or rhinoconjunctivitis substantially modifies this association.

Rhinitis: a complication to asthma

Allergy (Jan 2010)

Hansen JW, Nolte H, Backer V, Thomsen SF

Abstract
Background: Asthma and rhinitis often co-occur, and this potentially increases the disease severity and impacts negatively on the quality of life. We studied disease severity, airway responsiveness, atopy, quality of life and treatment in subjects with both asthma and rhinitis compared to patients with asthma or rhinitis alone.

Methods: We examined 878 patients: 182 with asthma, 362 with rhinitis and 334 with both asthma and rhinitis. All had a clinical interview concerning severity of symptoms, treatment, and quality of life, a skin prick test, a lung function test and a bronchial provocation with methacholine.

Results: Patients with both asthma and rhinitis had less severe asthma based on the frequency of respiratory symptoms compared to patients with asthma alone (55%vs 66%P = 0.01). On the contrary, they were more airway responsive (P<0.05) and had more perennial allergy (P<0.001). Asthmatics had poor perception of the general health, independent of rhinitis (P<0.001). No differences were found in asthma-specific quality of life, whereas rhinitis-specific quality of life was worse in those with both asthma and rhinitis compared to those with rhinitis alone (P<0.01). Subjects with both diseases were undertreated in 85% of the cases.

Conclusion: We encourage that these observations be used in the evaluation and treatment of patients with asthma and rhinitis and that they contribute to the understanding of asthma and rhinitis as a uniform airways disease.

Drug Profile: Montelukast in the treatment of asthma and beyond

Expert Review of Clinical Immunology
November 2009, Vol. 5, No. 6, Pages 639-658 , DOI 10.1586/eci.09.62
Zuzana Diamant†, Eva Mantzouranis and Leif Bjermer
†Author for correspondence


Asthma is a chronic inflammatory disease affecting over 300 million people worldwide. The common association with allergic rhinitis and the presence of proinflammatory cells and mediators in the circulation of patients qualify asthma as a systemic disease. This characteristic and the fact that the gold-standard therapy for persistent asthma, inhaled corticosteroids, cannot suppress all components of airway inflammation and fail to adequately penetrate into the small airways, warrant the quest for effective systemic anti-asthma therapies. This review describes the most important controlled studies of montelukast, a once-daily leukotriene receptor antagonist, in asthma and allergic rhinitis in both adults and children. Montelukast is a systemically active drug with a targeted, dual mechanism of action, acting both as a bronchodilator and anti-inflammatory. In patients of all ages, montelukast has shown a favorable safety profile and was well-tolerated. Both as monotherapy or in combination with inhaled corticosteroids, montelukast produced clinically relevant improvements in asthma-related parameters, including symptoms, lung function parameters, quality of life and the number of asthma exacerbations. Furthermore, bronchoprotective effects have been reported both against specific and nonspecific bronchoactive stimuli. Similarly, in patients with allergic rhinitis, montelukast produced substantial improvements in symptoms and quality of life. Long-term studies aimed to determine its effects on airway remodeling are still lacking.