Inflammation and allergic disease: An irrefutable combination

It is now clear that much of the pathology and clinical burden of allergic disease reflects the long-term consequences of chronic allergic inflammation at sites of persistent or repetitive exposure to allergens. This recognition has led to the creation of new diagnostic procedures, the development of improved therapeutic agents, and even to the formulation of new strategies to induce immunologic tolerance to the offending allergens and circumvent the deleterious effects of chronic inflammation. Nowhere is this relationship better illustrated than in chronic rhinosinusitis, a multifactorial inflammatory disease that is among the most common chronic conditions that afflict mankind. In this issue, Palmer et al.¹ reported the results of a U.S.-based cross-sectional, population-based survey in adult patients with symptoms of chronic rhinosinusitis, which provided a better understanding of the burden of disease attributable to this disorder. The study population consisted of a demographically and geographically representative sample of 10,336 adults recruited from a general pool of 4.3 million potentially susceptible subjects.¹ The investigators reported that 11.5% of the general U.S. adult population has chronic rhinosinusitis symptoms and that most report severe symptoms, lack of satisfaction with current treatment options, and a substantial adverse impact of the disease on daily functioning.¹

Another condition triggered by allergic inflammation and frequently associated with chronic rhinosinusitis is aspirin-exacerbated respiratory disease, also known as the Samter Triad, a chronic medical condition that consists of three clinical features: asthma, sinus disease with recurrent nasal polyps, and sensitivity to aspirin and other nonsteroidal anti-inflammatory drugs. In this issue, Laidlaw² provided a review of recent clinical research studies relevant to patients who have this disorder. Because of the importance of this article and its clinically useful implications, it was chosen for this issue's “For the Patient” section. This segment, found in the final pages of the print version of this issue and also available online, consists of a one-page article synopsis written in a readily comprehensible fashion to help patients better understand the content of the full article.

In transitioning from aspirin-exacerbated respiratory disease to asthma treatment, this issue features three original articles. In the first article, Ferro et al.³ studied the clinical burden of asynchrony in patients with asthma who used metered-dose inhalers (MDI) for control. The investigators defined asynchrony as any gap in timing between inhalation and actuation. Among 254 eligible patients, the investigators reported that 12.6% exhibited asynchrony and that the subjects afflicted with asynchrony had higher odds of an asthma exacerbation and lower odds of asthma control compared with patients without asynchrony.³ This study provided real-world evidence that asynchrony in MDI use among patients with asthma treated with controller MDIs was associated with a measurable clinical burden in terms of asthma exacerbations and control.

In the second article on asthma, Solanki et al.⁴ reported the effects of inhaled corticosteroids on serum periostin levels in adult patients with mild-to-moderate asthma. In a prospective, open-label, observational study of 40 adults with mild-to-moderate bronchial asthma initiated on inhaled corticosteroids, serum periostin, a marker of allergic inflammation and remodeling, was found to be elevated in bronchial asthma and was reduced by inhaled corticosteroid therapy.⁴ In the third article on asthma, Har and Lee⁵ studied systemic reaction rates in children with allergic asthma who were treated with omalizumab, subcutaneous immunotherapy, and a combined therapeutic regimen (i.e., omalizumab and subcutaneous immunotherapy). The investigators reported that children with moderate-to-severe persistent allergic asthma who received omalizumab or combination therapy had significantly lower systemic reaction rates compared with children with allergic asthma who received subcutaneous immunotherapy without omalizumab.⁵

The next group of articles focused on food allergy and begins with an epidemiologic report from Sha et al.,⁶ who performed a cross-sectional prevalence study of food allergies among children in Beijing. These investigators reported that the total prevalence of food allergies in children < 14 years of age was 3.2%.⁶ This article is followed by two review articles, the first by Greenhawt,⁷ who shared pearls and pitfalls of performing food challenges in infants. The second article, by Cook and Kim,⁸ deals with an update on peanut allergy and provided a better understanding of the safety and efficacy of oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy in patients afflicted with this condition.

On moving to the next group of articles, we focus on penicillin allergy and anaphylaxis. Kuruvilla et al.⁹ retrospectively evaluated the performance of direct oral amoxicillin challenges without preliminary skin testing in adult patients at low risk and labeled as being allergic to penicillin. The investigators reported that all 20 subjects who consented to amoxicillin challenge tolerated the procedure without the development of immediate or delayed hypersensitivity reactions.⁹ This study adds to the accumulating body of evidence that supports the safety and efficacy of direct provocative challenge without preliminary skin testing to exclude penicillin allergy in individuals at low risk.

In a study of anaphylaxis, Sundquist et al.¹⁰ examined risk factors for hospitalization and intensive care unit admission in adults and children by performing a retrospective chart review of patients with anaphylactic reactions who presented to the Albany Medical Center Emergency Department. The severity of symptoms and receiving multiple doses of epinephrine were identified as risk factors associated with hospitalization in both children and adults.¹⁰ Medicare/Medicaid insurance and cardiovascular or cutaneous symptoms were characteristics associated with intensive care unit admission.

An article by Barmettler et al.¹¹ shifts the focus to hereditary angioedema, a rare, autosomal dominant, genetic disorder associated with C1 inhibitor deficiency, which has been a recurrent topic in the Proceedings.^12–23 These investigators provided a rigorous review of the evolution of hereditary angioedema treatment options in the United States and discussed mechanisms of action, routes of administration, and efficacy of these therapies.¹¹

In summary, the collection of articles found within the pages of this issue provides further insight into the intersecting crossroads of genetics, the environment and chronic allergic inflammation which manifest as the allergic, cutaneous and respiratory disorders that afflict patients whom the allergist/immunologist serves. In particular, they exemplify how the complexities of chronic rhinosinusitis, asthma, food allergy, drug allergy, anaphylaxis, and hereditary angioedema continue to challenge the allergist/immunologist. In keeping with the overall mission of the Proceedings, which is to distribute timely information regarding advancements in the knowledge and practice of allergy, asthma, and immunology to clinicians entrusted with the care of patients, it is our hope that the articles found within this issue will help foster enhanced patient management and outcomes. On behalf of the Editorial Board, we hope that you are able to make practical use of the diversity of literature offered in this issue of the Proceedings.