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.

Skin testing in allergy.

Skin tests are used in addition to a directed history and physical examination to exclude or confirm immunoglobulin E (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: 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 that has been placed on the skin and gently lifting the epidermis up. Various devices are available for prick testing. Intracutaneous (intradermal) testing involves injecting a small amount of allergen 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, which causes vasodilatation, which leads to erythema (the flare). Prick testing methods are the initial technique for detecting the presence of IgE. These 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. 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 corresponding symptoms, the diagnosis of allergy can be made only by correlating skin testing results with the presence of clinical symptoms.

Allergen immunotherapy: definition, indications, 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 conjunctivitis, allergic asthma, and Hymenoptera hypersensitivity. Specific immunoglobulin E (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 adverse effects from pharmacotherapy; and (4) when avoidance is not possible. Several studies reported that immunotherapy in allergic rhinitis seems to prevent the development of new allergic sensitizations and/or new onset asthma. Humoral-, cellular-, and tissue-level changes occur with allergen immunotherapy, including induction of allergen-specific regulatory T and B cells, interleukin 10, and transforming growth factor ß production; suppression of T-helper type 2 cell proliferation; large increases in anti-allergen IgG4 antibodies; and reduction in basophil, mast cell, and eosinophil mediator release. Allergen immunotherapy can be administered either subcutaneously in the physician's office or sublingually by the patient at home. The use of immunotherapy in food allergy is still under investigation.

Classification of asthma.

Asthma is a chronic inflammatory disorder of the airways that results, 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. Asthma can be classified 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 (immunoglobulin E mediated), nonallergic (often triggered by viral upper respiratory tract infections or no apparent cause), occupational, aspirin-exacerbated respiratory disease, potentially 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, or beta2-adrenergic agonists, and to treatment for acid reflux and rhinosinusitis. Thus, cough variant asthma is in the differential diagnosis of chronic cough.

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. It is a medical emergency that requires immediate recognition and treatment. Albuterol in combination with ipratropium bromide in the emergency department (ED) has been shown to decrease the time spent in the ED and the hospitalization rates. The benefits of ipratropium are not sustained after admission to the hospital. 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 to 12 hours. Viral respiratory infections are a common trigger for acute asthma; other causes include medical nonadherence, allergen exposure (especially pets and mold [e.g., Alternaria species]) in individuals who are severely atopic, nonsteroidal anti-inflammatory exposure in patients with aspirin allergy, irritant inhalation (e.g., smoke, paint), exercise, and insufficient use of inhaled or oral corticosteroids. The patient's history should focus on the acute assessment of asthma control and morbidity, including current use of oral or inhaled corticosteroids; the number of hospitalizations, ED visits, intensive care unit admissions, and intubations; the frequency of albuterol use; the presence of nighttime symptoms; activity intolerance; current medications; exposure to allergens; and other significant medical conditions. Severe airflow obstruction may be predicted by accessory muscle use, difficulty speaking, refusal to recline < 30°, a pulse of >120 beats/min, and decreased breath sounds. 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 of >90% are reassuring, although CO2 retention and a low partial pressure of oxygen may be missed.

Urticaria and angioedema.

Urticaria, also known as hives, may affect up to 20% of the population at some time. Urticaria is described as pruritic erythematous, raised, circumscribed lesions with central pallor that blanch with pressure. Urticaria is closely associated with angioedema in 40% of individuals; approximately 10% of patients experience angioedema without urticaria. Urticarial lesions often are generalized, with multiple lesions in no specific distribution; angioedema tends to be localized and commonly affects the face (periorbital and perioral regions) or tongue. Urticaria is subdivided into acute and chronic urticaria based on the duration of symptoms. Acute urticaria lasts < 6 weeks, and an identifiable cause, such as food products, medications (aspirin, nonsteroidal anti-inflammatory drugs, antibiotics), or insect stings, may be discovered. Urticaria that lasts for >6 weeks is designated as chronic urticaria, and an etiology is seldom identified and thus considered spontaneous. Chronic urticaria may have an autoimmune basis. There is a well-documented association between autoimmune hypothyroidism (Hashimoto disease) and urticaria and angioedema, with a higher incidence of antithyroid (antithyroglobulin and antiperoxidase) antibodies in these patients, who are usually euthyroid. Furthermore, results of studies revealed a circulating immunoglobulin G (IgG) antibody directed against the high affinity IgE receptor alpha subunit IgE receptor (FcεRI) or IgE in 40-60% of patients with chronic urticaria. A stepwise approach to the treatment of urticarial is recommended with second-generation H1 antihistamines being the first line of therapy.

Eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is defined by symptoms related to esophageal dysfunction, persistent esophageal eosinophilia, and exclusion of other etiologies that may be contributing to the condition. EoE is different from erosive esophagitis. In children, symptoms vary by age groups, such as feeding disorders in 2 year olds; vomiting in 8 year olds; and abdominal pain, dysphagia, and/or food impaction in adolescents. Most adults present with dysphagia, food impaction, heartburn, or chest pain. Common endoscopic features in adults with EoE include linear furrows (creases that orient longitudinally), mucosal rings (esophageal "trachealization"), small-caliber esophagus, white plaques or exudates (which are microabscesses of eosinophils), and strictures. Children often present with similar endoscopic features, yet one-third of pediatric patients with EoE have a normal result in an endoscopic examination. Histologic features of EoE include increased intramucosal eosinophils in the esophagus (≥15 eosinophils per high power field), without similar findings in the stomach or duodenum. There also may be eosinophilic microabscesses. In addition to evidence of mast cell activation, mucosa from patients with EoE have increased levels of interleukin 5; supporting eosinophilia; and upregulation of gene expression of eotaxin-3, a chemokine important in eosinophil migration. The majority of patients have evidence of either aeroallergen and/or food sensitization. Dietary therapy is considered first-line therapy for patients with EoE because it is inexpensive and effective, without requiring pharmacologic therapy. Removal of food antigens has been shown to improve symptoms in patients with EoE. Topical corticosteroids improve esophageal eosinophilia and symptoms, and have become the criterion standard of pharmacotherapy.

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.

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 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 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.

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.

Asthma in the elderly: Current understanding and future research needs--a report of a National Institute on Aging (NIA) workshop.

Asthma in the elderly is underdiagnosed and undertreated, and there is a paucity of knowledge on the subject. The National Institute on Aging convened this workshop to identify what is known and what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of asthma in the elderly. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger patients, but comorbid illnesses and the psychosocial effects of aging might affect the diagnosis, clinical presentation, and care of asthma in this population. At least 2 phenotypes exist among elderly patients with asthma; those with longstanding asthma have more severe airflow limitation and less complete reversibility than those with late-onset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiologic mechanisms of asthma in the elderly are likely to be different from those seen in young asthmatic patients, and these differences might influence the clinical course and outcomes of asthma in this population.

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.

Advances in upper airway diseases and allergen immunotherapy in 2007.

The purpose of this review is to highlight important articles on upper airway diseases and immunotherapy that appeared in 2007. Advances in rhinitis include the realization that allergic rhinitis might be caused by local nasal IgE sensitization to aeroallergens in the absence of systemic evidence of IgE sensitization. After inhalation, allergens might reach systemic circulation. Epidemiologic studies continue to show that allergic rhinitis impairs school performance and is a risk factor for future asthma. New pathways are being identified in chronic sinusitis, as well as in different types of allergic ocular diseases. New treatments for patients with allergic rhinitis include use of beta-1,3-glucan, a mushroom product that can reduce allergic symptoms by inducing T(H)1 response, and olopatadine nasal spray. Studies on immunotherapy in 2007 suggest that sublingual immunotherapy induces similar immunologic alterations as those induced by subcutaneous immunotherapy, although to a lesser degree. Among allergists in the United States, there is a sizable variation in clinical practice, particularly related to concomitant administration of immunotherapy and beta-blockers, to administration of angiotensin-converting enzyme inhibitors, and to patients with HIV or autoimmune diseases. The combination of omalizumab with allergen subcutaneous immunotherapy can enhance clinical efficacy. Recombinant technology can modify allergen structure to prevent binding to IgE (allergenicity) while enhancing immunogenicity (stimulation of T cells), which might improve the safety and efficacy of immunotherapy.