COVID-19 vaccine-related presumed allergic reactions and second dose administration by using a two-step graded protocol.

Background: Acute allergic reactions to messenger RNA (mRNA) vaccines are rare but may limit public health immunization efforts. Objectives: To characterize suspected allergic reactions to the first dose of coronavirus disease 2019 (COVID-19) mRNA vaccine and to assess the safety and utility of a two-step graded-dose protocol for the second dose of the Pfizer-BioNTech vaccine in patients with a history of low suspicion of anaphylaxis to their first dose. Methods: This was a retrospective evaluation of referrals to the allergy and immunology clinic for a presumed allergic reaction to the first dose of the COVID-19 mRNA vaccine (Pfizer-BioNTech or Moderna) between December 17, 2020, and February 28, 2021. Recommendations for the second dose and outcomes were evaluated by trained board-certified allergists. Results: Seventy-seven patients presented with a Pfizer-BioNTech reaction (56 [72.7%]) or with a Moderna reaction (21 [27.3%]). Most patients (69.7%) had symptom onset within 4 hours. Most commonly reported symptoms were cutaneous (51.9%), cardiovascular (48.1%), and respiratory (33.8%) symptoms. Recommendations included to proceed with the single dose (70.1%), two-step graded dose (19.5%), or deferral (10.4%). Twelve of 15 patients completed the second dose with a graded-dose protocol. Of these patients, five reported at least one or more similar symptoms as experienced with their first dose. Conclusion: Of the patients with presumed allergic reactions to their first dose of COVID-19 mRNA vaccine, most were able to safely receive the second dose. For those with a low suspicion of anaphylaxis, the two-step graded protocol with the Pfizer-BioNTech vaccine was well tolerated. A graded-dose protocol could be an effective strategy for second-dose vaccination in those who may otherwise defer the second dose.

Prevalence and characterization of asthma in hospitalized and nonhospitalized patients with COVID-19.

BACKGROUND: The Centers for Disease Control and Prevention advises that patients with moderate to severe asthma belong to a high-risk group that is susceptible to severe coronavirus disease 2019 (COVID-19). However, the association between asthma and COVID-19 has not been well-established. OBJECTIVE: The primary objective was to determine the prevalence of asthma among patients with COVID-19 in a major US health system. We assessed the clinical characteristics and comorbidities in asthmatic and nonasthmatic patients with COVID-19. We also determined the risk of hospitalization associated with asthma and/or inhaled corticosteroid use. METHODS: Medical records of patients with COVID-19 were searched by a computer algorithm (March 1 to April 15, 2020), and chart review was used to validate the diagnosis of asthma and medications prescribed for asthma. All patients had PCR-confirmed COVID-19. Demographic and clinical features were characterized. Regression models were used to assess the associations between asthma and corticosteroid use and the risk of COVID-19-related hospitalization. RESULTS: Of 1526 patients identified with COVID-19, 220 (14%) were classified as having asthma. Asthma was not associated with an increased risk of hospitalization (relative risk, 0.96; 95% CI, 0.77-1.19) after adjusting for age, sex, and comorbidities. The ongoing use of inhaled corticosteroids did not increase the risk of hospitalization in a similar adjusted model (relative risk, 1.39; 95% CI, 0.90-2.15). CONCLUSIONS: Despite a substantial prevalence of asthma in our COVID-19 cohort, asthma was not associated with an increased risk of hospitalization. Similarly, the use of inhaled corticosteroids with or without systemic corticosteroids was not associated with COVID-19-related hospitalization.

Chapter 2: Skin testing in allergy.

Skin tests are used in addition to a directed history and physical exam to exclude or confirm IgE-mediated diseases such as allergic rhinitis, asthma, and anaphylaxis to aeroallergens, foods, insect venoms, and certain drugs. There are two types of skin testing used in clinical practice. These include percutaneous testing (prick or puncture) and intracutaneous testing (intradermal). Prick testing involves introducing a needle into the upper layers of the skin through a drop of allergen extract and gently lifting the epidermis up. Other devices are available for prick testing. Intracutaneous (intradermal) testing involves injecting a small amount of allergen (0.01-0.02 mL) into the dermis. The release of preformed histamine from mast cells causes increased vascular permeability via smooth muscle contraction and development of a wheal; inflammatory mediators initiate a neural reflex causing vasodilatation, leading to erythema (the flare). Prick testing methods are the initial technique for detecting the presence of IgE. They may correlate better with clinical sensitivity and are more specific but less sensitive than intradermal testing. Sites of skin testing include the back and the volar aspect of the arm. Although the back is more reactive, the difference is minimal. By skin testing on the arm, the patient can witness the emergence and often sense the pruritus of the skin test reaction. Because more patients are sensitized (have IgE antibodies and positive skin test reactions) than have current symptoms, the diagnosis of allergy can be made only by correlating skin testing results with the presence of clinical symptoms.

Chapter 3: Allergen immunotherapy: definition, indication, and reactions.

Specific allergen immunotherapy is the administration of increasing amounts of specific allergens to which the patient has type I immediate hypersensitivity. It is a disease modifying therapy, indicated for the treatment of allergic rhinitis, allergic asthma, and hymenoptera hypersensitivity. Specific IgE antibodies for appropriate allergens for immunotherapy must be documented. Indications for allergen immunotherapy include (1) inadequate symptom control despite pharmacotherapy and avoidance measures, (2) a desire to reduce the morbidity from allergic rhinitis and/or asthma or reduce the risk of anaphylaxis from a future insect sting, (3) when the patient experiences undesirable side effects from pharmacotherapy, and (4) when avoidance is not possible. Furthermore, patients may seek to benefit from economic savings of allergen immunotherapy compared with pharmacotherapy over time. Several studies have reported that immunotherapy in children with allergic rhinitis appears to prevent the development of new allergic sensitizations and/or new-onset asthma. Humoral, cellular, and tissue level changes occur with allergen immunotherapy including large increases in antiallergen IgG(4) antibodies, a decrease in the postseasonal rise of antiallergen IgE antibodies, reduced numbers of nasal mucosal mast cells and eosinophils, induction of Treg cells, and suppression of Th2 more than Th1 lymphocytes. There is a corresponding increase in IL-10 and transforming growth factor beta. In the United States, allergen immunotherapy is administered by the subcutaneous route in the physician's office, whereas primarily in some countries in Europe, it is administered for allergic rhinitis and asthma by the sublingual route by the patient at home.

Chapter 9: Asthma classification.

Asthma is a chronic inflammatory disorder of the airways resulting physiologically in hyperreactivity and clinically in recurrent episodes of wheezing, chest tightness, or coughing. Airway inflammation, smooth muscle contraction, epithelial sloughing, mucous hypersecretion, bronchial hyperresponsiveness, and mucosal edema contribute to the underlying pathophysiology of asthma. Diagnostic tests such as methacholine or mannitol challenges or spirometry (pre- and postbronchodilator responses) help to identify such underlying pathophysiology via assessments of bronchial hyperreactivity and lung mechanics but are imperfect and ultimately must be viewed in the context of a patient's clinical presentation including response to pharmacotherapy. The National Asthma Education and Prevention Program Expert Panel Report (2007) classifies asthma into either intermittent or persistent, and the latter is either mild, moderate, or severe. Some patients change in either direction from intermittent to persistent asthma. In addition, patients with asthma may be classified as allergic (IgE mediated), nonallergic (often triggered by viral upper respiratory tract infections or no apparent cause), occupational, aspirin-exacerbated respiratory disease, potentially (near) fatal, exercise induced, and cough variant asthma. In the latter, the patients have a nonproductive cough that responds to treatment for asthma but not with antibiotics, expectorants, mucolytics, antitussives, beta(2)-adrenergic agonists, treatment for acid reflux, or rhinosinusitis. Thus, cough variant asthma is in the differential diagnosis of chronic cough.

Chapter 14: Acute severe asthma (status asthmaticus).

Acute severe asthma, formerly known as status asthmaticus, is defined as severe asthma unresponsive to repeated courses of beta-agonist therapy such as inhaled albuterol, levalbuterol, or subcutaneous epinephrine. It is a medical emergency that requires immediate recognition and treatment. Oral or parenteral corticosteroids should be administered to all patients with acute severe asthma as early as possible because clinical benefits may not occur for a minimum of 6-12 hours. Approximately 50% of episodes are attributable to upper respiratory infections, and other causes include medical nonadherence, nonsteroidal anti-inflammatory exposure in aspirin-allergic patients, allergen exposure (especially pets) in severely atopic individuals, irritant inhalation (smoke, paint, etc.), exercise, and insufficient use of inhaled or oral corticosteroids. The patient history should be focused on acute severe asthma including current use of oral or inhaled corticosteroids, number of hospitalizations, emergency room visits, intensive-care unit admissions and intubations, the frequency of albuterol use, the presence of nighttime symptoms, exercise intolerance, current medications or illicit drug use, exposure to allergens, and other significant medical conditions. Severe airflow obstruction may be predicted by accessory muscle use, pulsus paradoxus, refusal to recline below 30°, a pulse >120 beats/min, and decreased breath sounds. Physicians' subjective assessments of airway obstruction are often inaccurate. More objective measures of airway obstruction via peak flow (or forced expiratory volume in 1 second) and pulse oximetry before oxygen administration usually are helpful. Pulse oximetry values >90% are less commonly associated with problems although CO(2) retention and a low Pao(2) may be missed.

Chapter 21: Urticaria and angioedema.

Urticaria, also known as hives, may affect up to 20% of the population at some time in their lives. Urticaria is characterized by extreme pruritus and described as erythematous, raised, circumscribed lesions with central pallor that blanch with pressure. The pathogenesis of urticaria involves mast cell activation, with subsequent release of histamine and other vasoactive mediators, leading to increased vascular permeability of postcapillary venules and development of edema, erythema, and pruritus. Urticaria is closely associated with angioedema in 40% of individuals; ∼10% of patients experience angioedema without urticaria. Urticarial lesions often are generalized with multiple lesions in no specific distribution; angioedema tends to be localized, commonly affecting the face (periorbital and perioral regions), tongue, uvula, soft palate or larynx, extremities, and genitalia. Urticaria is subdivided into acute and chronic urticaria based on duration of symptoms. Acute urticaria lasts <6 weeks and an identifiable cause may be discovered such as food products, medications (aspirin, nonsteroidal anti-inflammatory drugs, and antibiotics), or insect stings. Urticaria lasting >6 weeks is designated as chronic urticaria, and an etiology is seldom identified and thus considered idiopathic. Chronic urticaria may have an autoimmune basis. There is a well-documented association between autoimmune hypothyroidism (Hashimoto's disease) and urticaria and angioedema with higher incidence of antithyroid (antithyroglobulin and antiperoxidase) antibodies in these usually euthyroid patients. Furthermore, studies have revealed a circulating IgG antibody directed against the IgE receptor (F(Cε)RIα) or IgE in 40-60% of patients with chronic urticaria. Histamine 1-receptor antagonists (antihistamines) are initial therapy.

Advances in upper airway diseases and allergen immunotherapy in 2011.

The purpose of this review is to highlight recently published important articles on upper airway diseases and allergen immunotherapy. We review articles on rhinitis, sinusitis, conjunctivitis, and immunotherapy. New insights into epidemiology, pathophysiology, diagnosis, and therapy are described for each of the above diseases.

Advances in upper airway diseases and allergen immunotherapy.

The purpose of this review is to highlight recently published important articles on upper airway diseases and immunotherapy. We review articles on rhinitis, sinusitis, conjunctivitis, and immunotherapy. New insights into epidemiology, pathophysiology, diagnosis, and therapy are described for each of the above diseases. Regarding immunotherapy, we discuss numerous clinical trials on sublingual and subcutaneous immunotherapy, mechanisms of immunotherapy, safety, and use of modified allergens and biological agents for immunotherapy.

Improving asthma care for the elderly: a randomized controlled trial using a simple telephone intervention.

BACKGROUND: Several studies suggest that asthma is undertreated in the elderly population. OBJECTIVE: To determine if the use of a simple telephone intervention can improve asthma care in the elderly. METHODS: Fifty-two elderly subjects with asthma who required their rescue inhalers more than twice a week and had at least one emergency department or urgent care visit in the previous year were randomized to an intervention or control group. All subjects received two telephone calls over a 12-month period. The intervention group received an asthma-specific questionnaire and the control group received a general health questionnaire. Medication use and health care utilization were evaluated at the beginning and end of a 12-month period. RESULTS: The study was completed by 23 control and 25 intervention subjects. Baseline data were similar in both groups. After 12 months, 72% (n = 18) of the intervention group were on an inhaled corticosteroid compared with 40% (n = 10) of the control group (p = 0.08). The intervention group had fewer emergency department visits when compared with the control group (p = 0.21). Sixty-four percent (n = 16) of the intervention group had an asthma action plan compared with 26% (n = 6) in the control group (p = 0.01). CONCLUSION: This study suggests that asthma care in the elderly can be improved using a simple telephone intervention. CLINICAL IMPLICATIONS: Clinicians need to recognize that under treatment of asthma in the elderly still exists and to use alternative methods such as a simple telephone questionnaire to improve care in this population.

Prevalence of obstructive airways disease in the disadvantaged elderly of Chicago.

The prevalence of obstructive airways disease in the disadvantaged elderly population is underestimated. Consequently, asthma may be suboptimally managed in this population leading to poorer symptom control and quality of life in this group. The objective of this study was to estimate the prevalence of obstructive airways disease (OAD) in a disadvantaged elderly population. A cross-sectional study was conducted in which we interviewed older adults at centers subsidized by the Chicago Department on Aging. Participants were individuals who agreed to complete a five-page questionnaire about their health. Three hundred eighty individuals agreed to fill out a questionnaire about their health. The mean and median age was 74 years. There were 38 (10%) individuals with self-report of doctor-diagnosed asthma, 40 (11%) individuals with doctor-diagnosed chronic bronchitis, and 14 (4%) individuals with doctor-diagnosed emphysema. They had these diagnoses for a mean of 10.4 years (range, 0-50 years). Thirty-three (9%) individuals who did not have doctor-diagnosed disease had wheezing or whistling when they breathed and shortness of breath or cough with exercise. Of those 125 individuals with doctor-diagnosed disease or symptoms suggestive of OAD, only 22 (18%) individuals took their prescribed medications on a regular basis. Symptoms of OAD appear to be common in the disadvantaged elderly in Chicago. Based on these results, 92 (24%) individuals had doctor-diagnosed asthma, chronic bronchitis, and/or emphysema. The majority did not take their medications regularly. Another 33 (9%) individuals had symptoms compatible with OAD that had not been diagnosed or treated.

Update on efficacy of allergen immunotherapy for allergic rhinitis and asthma.

Specific allergen immunotherapy (IT) has long been used to treat allergic rhinitis and asthma. Review of the literature from the past 5 years continues to support this use of IT as the only disease-modifying treatment of allergic disease currently available. In addition, studies suggest that allergen IT may prevent the progression of allergic disease. In monosensitized patients, IT may prevent polysensitization. In younger patients with allergic rhinitis only, IT may prevent the new onset of asthma. Although these studies require further validation, the evidence is important enough to consider disease prevention as one of the indications for prescribing allergen IT.