Global strategy for asthma management and prevention

Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations.

In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease.

This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work.

The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available.

Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed.

The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

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Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

SUMMARY OF APPROACH The approach to surgery in the patient with COPD is summa-rized below. Surgery Definitely indicated Lung resection. Pulmonary function studies should be performedbefore lung resection. Simple spirometry has the greatest utilityin documenting physiologic operability. FEV, > 2 L in an adultman or > 60% of predicted is acceptable for pneumonectomy.Values below this suggest that further studies, such as split func-tion assessment by quantitative lung scintigraphy and exercisetesting, are warranted.FEV, predicted after lung resection to be less than 40 to 50%of normal for the patient’s sex, age, and height suggests highermorbidity and mortality. An exercise 90, of less than 10 to 15ml/min per kg of body weight is associated with higher mor-bidity and mortality after lung resection.All elective surgery Prophylaxis against deep venous throm-bosis should be given before most procedures that will requirepostoperative bed rest or significantly reduce mobility. Heparinin low doses seems well accepted for most procedures. Externalpneumatic compression of the lower legs can be used when anti-coagulants are contraindicated.

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Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease

Authors Jan L. Brozek, MD, PhD – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada Jean Bousquet, MD, PhD – Service des Maladies Respiratoires, Hopital Arnaud de Villeneuve, Montpellier, France, INSERM, CESP U1018, Respiratory and Environmental Epidemiology Team, France, and WHO Collaborating Center for Rhinitis and Asthma Carlos E. Baena-Cagnani, MD – Faculty of Medicine, Catholic University of Cordoba, Cordoba, Argentina Sergio Bonini, MD – Institute of Neurobiology and Molecular Medicine – CNR, Rome, Italy and Department of Medicine, Second University of Naples, Naples, Italy G. Walter Canonica, MD – Allergy & Respiratory Diseases, DIMI, Department of Internal Medicine, University of Genoa, Genoa, Italy Thomas B. Casale, MD – Division of Allergy and Immunology, Department of Medicine, Creighton University, Omaha, Nebraska, USA Roy Gerth van Wijk, MD, PhD – Section of Allergology, Department of Internal Medicine, Erasmus Medical Centre, Rotterdam, the Netherlands Ken Ohta, MD, PhD – Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan Torsten Zuberbier, MD – Department of Dermatology and Allergy, Charite Universitatsmedizin Berlin, Berlin, Germany Holger J. Schunemann, MD, PhD, MSc – Department of Clinical Epidemiology & Biostatistics and Medicine, McMaster University, Hamilton, Canada

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Allergic Rhinitis and Its Impact on Asthma

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71142-9.pdf

Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.

A group of investigators interested in the standardization of inhalation challenge techniques was selected by the program directors of the Asthma and Allergic Disease Centers (AADC). This effort has been assisted by the National Institute of Allergic and Infectious Diseases of the National Institutes of Health. At the last meeting of the panel on February 15, 19’75, criteria for procedures and materials used were suggested in order to standardize bronchial inhalation challenges as they pertain to allergic disease.

https://www.jacionline.org/article/0091-6749(75)90107-4/pdf

Standardization of bronchial inhalation challenge procedures

The clinical benefit and steroid-sparing effect of treatment with the anti-immunoglobulin-E (IgE) antibody, omalizumab, was assessed in patients with moderate-to-severe allergic asthma. After a run-in period, 546 allergic asthmatics (aged 12-76 yrs), symptomatic despite inhaled corticosteroids (500-1,200 microg daily of beclomethasone dipropionate), were randomized to receive double-blind either placebo or omalizumab every 2 or 4 weeks (depending on body weight and serum total IgE) subcutaneously for 7 months. A constant beclomethasone dose was maintained during a 16-week stable-steroid phase and progressively reduced to the lowest dose required for asthma control over the following 8 weeks. The latter dose was maintained for the next 4 weeks. Asthma exacerbations represented the primary variable. Compared to the placebo group, the omalizumab group showed 58% fewer exacerbations per patient during the stable-steroid phase (p<0.001). During the steroid-reduction phase, there were 52% fewer exacerbations in the omalizumab group versus the placebo group (p<0.001) despite the greater reduction of the beclomethasone dosage on omalizumab (p<0.001). Treatment with omalizumab was well tolerated. The incidence of adverse events was similar in both groups. These results indicate that omalizumab therapy safely improves asthma control in allergic asthmatics who remain symptomatic despite regular use of inhaled corticosteroids and simultaneous reduction in corticosteroid requirement.

https://erj.ersjournals.com/content/erj/18/2/254.full.pdf

The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics

Ninety-eight subjects underwent methacholine (Mecholyl) aerosol challenge at a concentration of 5 mg/ml. All atopic groups differed significantly in their bronchial response to Mecholyl compared to nonatopic control subjects. Nineteen normal subjects had a mean decrease of 11.4% in forced expiratory volume in one second (FEV1) with 128 Mecholyl inhalations and 2 decreased by greater than 20%. Fifteen of 27 allergic rhinitis patients had a positive response to Mecholyl as defined by a decrease in FEV1 greater than 20%. Four of these responders developed greater diminution in FEV1 response with additional Mecholyl inhalations in a manner similar to that seen in the asthmatic patients. Eighteen current asthmatics showed the greatest bronchial sensitivity to Mecholyl with a mean 33% decrease in FEV1 at 4.5 inhalations. One hundred per cent of current asthmatics and 82% (28 of 34) of former asthmatics (free of asthma symptoms for 1 to 20 yr) showed positive response to Mecholyl. A 20% decrease in FEV1 with a total of 20 inhalations or less is consistent with a diagnosis of "current asthma," and even 20 of 34 former asthmatics responded in this manner. The Mecholyl aerosol test can be used to diagnose previous and current asthma and may be of value in predicting asthma in hay fever patients.

https://www.jacionline.org/article/0091-6749(75)90061-5/pdf

Bronchial sensitivity to methacholine in current and former asthmatic and allergic rhinitis patients and control subjects.

Background Rush immunotherapy (RIT) presents an attractive alternative to standard immunotherapy. However, RIT carries a much greater risk of acute allergic reactions, including anaphylaxis. Objectives We hypothesized that omalizumab, a humanized monoclonal anti-IgE antibody, would be effective in enhancing both safety and efficacy of RIT. Methods Adult patients with ragweed allergic rhinitis were enrolled in a 3-center, 4-arm, double-blind, parallel-group, placebo-controlled trial. Patients received either 9 weeks of omalizumab (0.016 mg/kg/IgE [IU/mL]/mo) or placebo, followed by 1-day rush (maximal dose 1.2-4.0 μg Amb a 1) or placebo immunotherapy, then 12 weeks of omalizumab or placebo plus immunotherapy. Results Of the 159 patients enrolled, 123 completed all treatments. Ragweed-specific IgG levels increased >11-fold in immunotherapy patients, and free IgE levels declined >10-fold in omalizumab patients. Patients receiving omalizumab plus immunotherapy had fewer adverse events than those receiving immunotherapy alone. Post hoc analysis of groups receiving immunotherapy demonstrated that addition of omalizumab resulted in a 5-fold decrease in risk of anaphylaxis caused by RIT (odds ratio, 0.17; P = .026). On an intent-to-treat basis, patients receiving both omalizumab and immunotherapy showed a significant improvement in severity scores during the ragweed season compared with those receiving immunotherapy alone (0.69 vs 0.86; P = .044). Conclusion Omalizumab pretreatment enhances the safety of RIT for ragweed allergic rhinitis. Furthermore, combined therapy with omalizumab and allergen immunotherapy may be an effective strategy to permit more rapid and higher doses of allergen immunotherapy to be given more safely and with greater efficacy to patients with allergic diseases.

Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis

One hundred seven pairs of twins, sixty-one MZT and forty-six DZT, were investigated for allergic disease by a questionnaire, reaginic antibody levels, bronchial reactivity to inhaled methacholine, and skin test responses. Intrapair correlation coefficients (ri) of measured clinical markers of atopy were determined and a heritability analysis was performed. The intrapair correlation coefficient for serum IgE was 0.82 for MZT and 0.52 for DZT. The methacholine area demonstrated greater correlation in MZT with an ri of 0.67 compared to 0.34 for DZT. The total ISTS had an intrapair correlation coefficient of 0.82 in MZT and 0.46 in DZT. Our analysis demonstrates that methacholine sensitivity, total serum IgE levels, and total skin test scores to be heritable traits and suggests a genetic contribution to their expression.

https://www.jacionline.org/article/S0091-6749(84)80018-4/pdf

Robert G. Townley

Papers

Standardization of bronchial inhalation challenge procedures

The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics

Bronchial sensitivity to methacholine in current and former asthmatic and allergic rhinitis patients and control subjects.

Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis

Genetic analysis of allergic disease in twins