The Joint Task Force on Practice Parameters GRADE guidelines for the medical management of chronic rhinosinusitis with nasal polyposis.

These evidence-based guidelines support patients, clinicians, and other stakeholders in decisions about the use of intranasal corticosteroids (INCS), biologics, and aspirin therapy after desensitization (ATAD) for the management of chronic rhinosinusitis with nasal polyposis (CRSwNP). It is important to note that the current evidence on surgery for CRSwNP was not assessed for this guideline nor were management options other than INCS, biologics, and ATAD. The Allergy-Immunology Joint Task Force on Practice Parameters formed a multidisciplinary guideline panel balanced to include the views of multiple stakeholders and to minimize potential biases. Systematic reviews for each management option informed the guideline. The guideline panel used the Grading of Recommendations Assessment, Development and Evaluation approach to inform and develop recommendations. The guideline panel reached consensus on the following statements: (1) In people with CRSwNP, the guideline panel suggests INCS rather than no INCS (conditional recommendation, low certainty of evidence). (2) In people with CRSwNP, the guideline panel suggests biologics rather than no biologics (conditional recommendation, moderate certainty of evidence). (3) In people with aspirin (nonsteroidal anti-inflammatory drug)-exacerbated respiratory disease, the guideline panel suggests ATAD rather than no ATAD (conditional recommendation, moderate certainty of evidence). The conditions for each recommendation are discussed in the guideline.

Topical corticosteroids for chronic rhinosinusitis with nasal polyposis: GRADE systematic review and network meta-analysis.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is associated with a significant disease burden. The optimal use of and administration route for intranasal corticosteroids (INCS) when managing CRSwNP are unclear. OBJECTIVE: We systematically synthesized the evidence addressing INCS for CRSwNP. METHODS: We searched studies archived in Medline, Embase, and Central from database inception until September 1, 2021, for randomized controlled trials comparing INCS using any delivery method to placebo or other INCS administration types. Paired reviewers screened records, abstracted data, and rated risk of bias (CLARITY revision of Cochrane Risk of Bias version 1 tool) independently and in duplicate. We synthesized the evidence for each outcome using random effects network meta-analyses. We critically appraised the evidence following the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) approach. RESULTS: We analyzed 61 randomized controlled trials (7176 participants, 8 interventions). Sinusitis-related quality of life might improve with INCS rinse (mean difference [MD] -6.83, 95% confidence interval [CI] -11.94 to -1.71) and exhalation delivery system (EDS) (MD -7.86, 95% CI -14.64 to -1.08) compared to placebo (both low certainty evidence). Nasal obstruction symptoms are likely improved when receiving INCS via stent/dressing (MD -0.31, 95% CI -0.54 to -0.08), spray (MD -0.51, 95% CI -0.61 to -0.41), and EDS (MD -0.35, 95% CI -0.51 to -0.18) (all moderate to high certainty) compared to placebo. We found no important differences in adverse effects among interventions (moderate certainty for INCS spray, very low to low certainty for others). CONCLUSIONS: Multiple delivery forms of INCS are viable therapeutic options for CRSwNP, resulting in improvement of patient-important outcomes. INCS via stent, spray, and EDS appear to be beneficial across the widest range of considered outcomes.

Effect of omalizumab on outcomes in patients with aspirin-exacerbated respiratory disease.

Background: The current treatment for patients with aspirin-exacerbated respiratory disease (AERD) who have uncontrolled asthma or chronic rhinosinusitis is aspirin desensitization. For patients who are unable to undergo or do not benefit from aspirin desensitization, treatment with biologics is an option, although efficacy data for AERD is scarce. Objective: We reported a series of patients with AERD who were started on omalizumab and measured the outcomes to assess improvement. Methods: Adult patients with AERD who were initiated on omalizumab from January 2007 to January 2018 were included. We compared outcomes 6-12 months before initiating biologic therapy and during the last 6-12 months while they were on biologic therapy. Our study investigated the number of oral steroid courses, short-acting beta-agonists (SABA), antibiotics for sinusitis or pneumonia, emergency department visits, hospitalizations, pulmonary function tests, and changes in controller medications. Results: Twenty-nine patients were placed on omalizumab. Sixty-two percent demonstrated a reduction in the number of steroid courses (p = 0.0014) and number of SABA canisters used (p = 0.0005) during their last 12 months while on omalizumab. Eighty-six percent of the patients with AERD and on omalizumab demonstrated either a decrease in the number of steroid courses or number of SABA canisters used in the last year of the study. The patients with AERD and with concomitant immunoglobulin E (IgE) mediated respiratory disease showed a statistically significant reduction in the number of steroid courses and number of SABA canisters used while on omalizumab for 1 year (p = 0.002 and p = 0.005, respectively), whereas those without concomitant IgE-mediated respiratory disease did not have a substantial reduction in steroids or SABA canisters used. Conclusion: Our case series reported that omalizumab could effectively be used as an adjunct treatment for AERD, but additional larger and longitudinal studies are needed to corroborate these findings.

A 45-year-old man with elevated levels of immunoglobulin A.

Quantitative immunoglobulin tests are often ordered as part of the initial evaluation for suspected immune deficiency. Although alterations in immunoglobulin levels can explain recurrent infections, in a patient without symptoms, there are a variety of other factors that can alter immunoglobulin levels. Common causes for elevated immunoglobulin A levels include malignancy and hepatic impairment in addition to a variety of infiltrative, infectious, and inflammatory diseases. We present a case of a 45-year-old man with a history of recurrent sinopulmonary symptoms without bacterial infection found to have an isolated elevated level of immunoglobulin A.

Making Sense of Metal Allergy and Hypersensitivity to Metallic Implants in Relation to Hand Surgery.

All metals implanted into a biological system undergo some degree of corrosion depending upon its composition. The electrochemical process of corrosion produces free metal ions, which may activate the host's immune system through a variety of mechanisms. Whereas dermal metal hypersensitivity is common, affecting 10% to 15% of the population, the immune reaction from implanted metals is much less common (< 0.1%), but has been associated with metal allergy and hypersensitivity producing a multitude of patient symptoms. Superficial symptoms may be mild to severe forms of dermatitis, urticaria, pruritus, and vasculitis, whereas deep sequelae include metallosis-related pseudotumor, implant loosening, and joint stiffness. Currently, there are clinical tests to evaluate patients for metal hypersensitivity, but there is little agreement regarding the ideal timing and clinical situation prompting the work-up of a patient for a metal allergy or hypersensitivity. An understanding of the epidemiology, etiology, basic science, diagnostic testing, and treatment of patients with suspected metal allergy, as it pertains to the current literature, will aid orthopedic and plastic surgeons of all subspecialties in the management of patients requiring metallic implants.

Anaphylaxis in a health maintenance organization: International Classification of Diseases coding and epinephrine auto-injector prescribing.

BACKGROUND: Accurate estimates of the incidence of anaphylaxis are limited. Current International Classification of Diseases, Ninth Revision (ICD-9) codes complicate accurate diagnosis of anaphylaxis and assessment of appropriate epinephrine prescribing. OBJECTIVE: To quantify the incidence and demographic character of patients with anaphylaxis-related ICD-9 codes in a large health maintenance organization and analyze epinephrine prescribing and dispensing rates. METHODS: All patients included had at least 12 months of continuous membership over a 4-year period from January 1, 2008 to December 31, 2012 and were selected based on anaphylaxis-related ICD-9 codes (N = 159,172). This algorithm was extrapolated from a previous study that used expanded ICD-9 codes to identify more cases of anaphylaxis. Individual chart reviews found that many expanded ICD-9 codes represented unconfirmed cases of anaphylaxis and therefore were excluded, resulting in analysis of 52,405 patients. RESULTS: Incidence of anaphylaxis over 4 years was 2.07%, with female predominance (56.5%) over male predominance (43.5%). Epinephrine was prescribed in 16.2% of total cases. Highest rates of epinephrine prescription were for traditional ICD-9 codes 995.0 (other anaphylactic shock) and 995.60 to 995.69 (anaphylactic shock caused by food) at 49.3% and 58.6%, respectively. Of the cases in which an epinephrine auto-injector was prescribed, it was dispensed 95.9% of the time, independent of copayment amount. CONCLUSION: Low epinephrine auto-injector prescribing rates in cases of anaphylaxis suggest the continued difficulty in the diagnosis of anaphylaxis and could result in suboptimal treatment of potential future episodes.

A proposed model to study immunologic changes during chronic rhinosinusitis exacerbations: data from a pilot study.

BACKGROUND: One way to gain insight into the pathophysiology of chronic rhinosinusitis (CRS) is to study the immunologic changes that occur with exacerbation. This study describes the immunologic changes during CRS exacerbation METHODS: We performed a prospective study to investigate the immunologic changes seen during exacerbation of CRS with nasal polyposis. We recruited adult subjects who met clinical criteria for CRS with sinus CT scan within the past 5 years with Lund-Mackay score of >5 and nasal polyps. Subjects underwent a baseline visit with collection of nasal secretion and nasal wash. With acute worsening of symptoms, subjects underwent 6 near-consecutive-day collections and one follow-up collection 2 weeks later. IL-6, IL-33, eosinophil major basic protein (MBP), eosinophil-derived neurotoxin (EDN), myeloperoxidase (MPO), and uric acid were measured on the nasal samples from each visit. RESULTS: A total of 10 subjects were recruited and 9 had acute worsening of CRS during the study period. Eight of the nine subjects were women and ages ranged from 26 to 56 years. At baseline, most inflammatory parameters were low and eight of the nine subjects were on intranasal corticosteroids. Compared with baseline measurements, IL-6, MBP, MPO, EDN, and uric acid were significantly elevated during CRS exacerbation. Levels of IL-6 and MBP (r = 0.47) levels as well as IL-6 and MPO (r = 0.75) were both significantly correlated (p < 0.01). CONCLUSION: Prospective study of CRS exacerbations is feasible and provides insights into the immunologic mechanisms of CRS.

Outcomes of stepping down asthma medications in a guideline-based pediatric asthma management program.

BACKGROUND: Little is known about outcomes after stepping down asthma medications within an asthma management program. OBJECTIVE: To determine outcomes of stepping down asthma medications in a pediatric asthma management program. METHODS: We performed a retrospective study of 5- to 18-year-old children with asthma in an integrated primary care practice in the United States. Data were included on participants from March 1, 2009, until December 31, 2011. We first determined whether a child was eligible for step down and next recorded whether a step-down attempt was made and if the attempt was successful. In addition to descriptive statistics for the sample demographics and the outcomes of stepping down, univariate and multivariate analyses were performed to determine predictors of successful asthma medication step-down attempts. RESULTS: Of the 477 children sampled for this study, 264 (55.3%) had a guideline-eligible opportunity to step down asthma medications. An attempted step down occurred in only 89 (33.7%) of children who had guideline-eligible opportunities. A total of 166 children (34.8%) attempted a step down of asthma medication at least once (including those guideline ineligible to step down). Of children with follow-up, 96 (71.6%) of step-down attempts were successful. Time of year (any season except fall) when the step down was attempted predicted successful step down in univariate and multivariate analysis (odds ratio = 3.81; 95% confidence interval, 1.23-11.85; P = .02). Being guideline eligible for step down predicted successful step down in univariate analysis only (odds ratio = 2.51; 95% confidence interval, 1.16-5.43; P = .02). CONCLUSION: Our findings from this sample of children participating in an asthma management program suggest that stepping down asthma medication based on National Asthma Education and Prevention Program 3 guidelines is frequently successful.

Anaphylaxis: diagnostic criteria and epidemiology.

Evaluation of anaphylaxis is a common reason for emergency department referral to an allergist. Establishing unified diagnostic criteria has been an evolving process with the most recent definition proposed by the Second Symposium on the Definition and Management of Anaphylaxis convened by the National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network. Proper identification of these patients in the emergency department allows for the opportunity to dispense potentially life-saving epinephrine autoinjectors, provide education, and allergist referral. Future epidemiological studies are likely to be impacted as the definition of anaphylaxis becomes more unified.

The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Current asthma guidelines suggest that patients and their providers consider decreasing or stopping controller medications when asthma is stable. OBJECTIVE: We sought to estimate the risk of asthma exacerbation in patients who stop low-dose inhaled corticosteroids (ICSs) compared with those who continue ICSs in randomized controlled trials. METHODS: We identified relevant trials from a systematic review of English-language and non-English-language articles using MEDLINE, EMBASE, and CENTRAL (inception to January 21, 2012). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included randomized controlled trials with a stable asthma run-in period of 4 weeks or more, an intervention to stop or continue ICSs, and a follow-up period of at least 3 months. We pooled results using a random-effects meta-analysis. RESULTS: The search strategy identified 1798 potential articles, of which 172 were reviewed at the full-text level and 7 met the criteria for inclusion. The relative risk for an asthma exacerbation in patients who stopped ICSs compared with those who continued use was 2.35 (95% CI, 1.88-2.92; P < .001; I(2) = 0%), as determined by using data pooled from trials with a mean follow-up of 27 weeks. The pooled absolute risk difference for an asthma exacerbation was 0.23 (95% CI, 0.16-0.30; P < .001; I(2) = 44%). Patients who discontinued ICSs also had a decreased FEV1 of 130 mL (95% CI, 40-210 mL; P = .003; I(2) = 53%), a decreased mean morning peak expiratory flow of 18 L/min (95% CI, 6-29 L/min; P = .004; I(2) = 82%), and an increased mean standardized asthma symptom score of 0.43 SDs (95% CI, 0.28-0.58 SDs; P < .001; I(2) = 0%). CONCLUSION: Patients with well-controlled asthma who stop regular use of low-dose ICSs have an increased risk of an asthma exacerbation compared with those who continue ICSs.

Length of stay in skilled nursing facilities is longer for patients with dementia.

Studies estimate prolonged stays in acute and sub-acute facilities for patients with dementia. Actuarial projections suggest prolonged stays in long term care facilities for patients with dementia. To test these predictions, we assessed whether patients with dementia stay in skilled nursing facilities (SNF) longer than patients without dementia. We obtained medical records of 5,373 residents discharged from a SNF between 1996 and 2001. Residents were identified as having dementia by ICD-9 codes. Age, sex and length of stay (LOS), measured in days from admission to discharge or death, were gathered. Mean LOS for patients with dementia (92.7 +/- 313.0, n = 758) was significantly longer than non-demented patients (29.7 +/- 136.8, n = 4615, p < 0.001). In a subset of individuals who stayed until death, the mean LOS for patients with dementia (202.9 +/- 528.6, n = 195) also was significantly longer than for non-demented patients (91.8 +/- 300.5, n = 610, p < 0.001). LOS was increased for demented patients even within age groups. Thus, patients with dementia stay in SNFs significantly longer from entry until discharge or death. It is likely that demented patients enter for non-physical, cognitive related reasons. These results may help families and institutions plan for long-term care.