Andrej A. Petrov

A Novel Scoring System to Distinguish Vocal Cord Dysfunction From Asthma

BACKGROUND Vocal cord dysfunction is often misdiagnosed and mistreated as asthma, which can lead to increased and unnecessary medication use and increased health care utilization. OBJECTIVE To develop a valid scoring index that could help distinguish vocal cord dysfunction from asthma. METHODS We compared the demographics, comorbidities, clinical symptoms, and symptom triggers of subjects with vocal cord dysfunction (n = 89) and those with asthma (n = 59). By using multivariable logistic regression, we identified distinguishing features associated with vocal cord dysfunction, which were weighted and used to generate a novel score. The scoring index also was tested in an independent sample with documented vocal cord dysfunction (n = 72). RESULTS We identified symptoms of throat tightness and dysphonia, the absence of wheezing, and the presence of odors as a symptom trigger as key features of vocal cord dysfunction that distinguish it from asthma. We developed a weighted index based on these characteristics, the Pittsburgh Vocal Cord Dysfunction Index. By using a cutoff of ≥4, this index had good sensitivity (0.83) and specificity (0.95) for the diagnosis of vocal cord dysfunction. The scoring index also performed reasonably well in the independent convenience sample with laryngoscopy-proven vocal cord dysfunction and accurately made the diagnosis in 77.8% of subjects. CONCLUSION The Pittsburgh Vocal Cord Dysfunction Index is proposed as a simple, valid, and easy-to-use tool for diagnosing vocal cord dysfunction. If confirmed by a prospective evaluation in broader use, it may have significant clinical utility by facilitating a timely and accurate diagnosis of vocal cord dysfunction, thereby preventing misdiagnosis and mistreatment as asthma. Future prospective validation studies will need to be performed.

Omalizumab and hypersensitivity reactions.

Purpose of reviewOmalizumab, a monoclonal anti-IgE antibody, is currently indicated for the treatment of moderate-to-severe allergic asthma. We have reviewed the published studies and case reports of off-label omalizumab use in the prevention of IgE-mediated hypersensitivity reactions of various causes. Additionally, we have reviewed anaphylaxis associated with omalizumab treatment. Recent findingsMany case reports and smaller studies have reported the efficacy of omalizumab in the prevention of various hypersensitivity and anaphylactic reactions with or without known trigger. One randomized study has showed partial improvement in the tolerance of peanuts in peanut-allergic patients with anti-IgE therapy. Furthermore, several randomized, placebo-controlled studies and case reports have demonstrated that omalizumab in combination with allergen or venom immunotherapy decreases the incidence of systemic hypersensitivity reactions and may improve the clinical outcomes. Finally, review of the data documents low risk of anaphylaxis with omalizumab use, with one study demonstrating successful desensitization to this medication. SummaryThe available studies indicate that omalizumab is effective and well tolerated in decreasing hypersensitivity reactions associated with allergen immunotherapy in patients with allergic rhinitis and mild-to-moderate asthma. Additionally, omalizumab may represent a promising therapy of anaphylaxis with or without known trigger, which should be further investigated with randomized studies. Moreover, additional research is needed to elucidate the mechanism of anaphylaxis with the medication itself.

The morbidity and cost of vocal cord dysfunction misdiagnosed as asthma.

BACKGROUND Vocal cord dysfunction (VCD) is frequently misdiagnosed and mistreated as asthma, which leads to morbidity secondary to unnecessary medication use and increased health care utilization. OBJECTIVE We identified discriminating symptoms and triggers, and analyzed the costs, morbidity, and health care burden associated with misdiagnosis of VCD as asthma. We sought to determine if current measures of asthma control contributed to these findings. We evaluated if a simple set of breathing exercises would be an effective low-cost treatment option for those with VCD. METHODS We compared the demographics, comorbidities, clinical symptoms, and symptom triggers of subjects with VCD misdiagnosed as asthma compared with those not misdiagnosed as asthma. Costs secondary to asthma misdiagnosis were quantified, and the effectiveness of breathing exercises as a treatment option was evaluated. RESULTS We identified symptoms of shortness of breath, wheezing, chest tightness, and a trigger of exercise as being more common in the subjects with VCD misdiagnosed as asthma. Asthma medication use and health care utilization and costs were also higher in this group. The subjects with VCD had Asthma Control Questionnaire scores that labelled them as having uncontrolled asthma. Breathing exercises appeared to offer an inexpensive and effective treatment option for subjects with VCD. CONCLUSION Misdiagnosis of VCD as asthma leads to significant morbidity and increased costs, and misuse of measures of asthma control may be contributing to these findings. Timely and accurate diagnosis of VCD and the use of breathing exercises have the potential to eliminate or minimize the burdens on the patient and the health care system.

Successful desensitization of three patients with hypersensitivity reactions to omalizumab.

BACKGROUND Omalizumab is prescribed as a step-up therapy for patients with moderate to severe allergic asthma uncontrolled on high-dose inhaled corticosteroids and long acting beta agonists. However, hypersensitivity reactions may lead to its discontinuation and subsequent worsening or loss of asthma control. No successful desensitization protocols to omalizumab have been previously reported. OBJECTIVE We aimed to determine the efficacy and safety of a novel one-day outpatient omalizumab desensitization protocol for patients with hypersensitivity reactions to omalizumab. METHODS We retrospectively assessed the efficacy of omalizumab desensitization protocol performed in a university allergy-immunology clinic from July 2009 to July 2010. RESULTS We successfully desensitized 3 patients with moderate-severe asthma to omalizumab. After desensitization all patients had improvement in asthma control and were able to discontinue or decrease chronic systemic steroid therapy. CONCLUSIONS This novel outpatient omalizumab desensitization protocol was a safe and effective approach for the treatment of omalizumab hypersensitivity in patients with moderate to severe allergic asthma who required omalizumab therapy.

Clopidogrel Hypersensitivity: A Novel Multi-Day Outpatient Oral Desensitization Regimen

BACKGROUND Clopidogrel hypersensitivity has posed a problem for the acute treatment and long-term care of a particular patient population with coronary artery disease and stent placement. Patients with clopidogrel hypersensitivity have had an increased risk of hypersensitivity reactions, including anaphylaxis, if they ingest clopidogrel without undergoing an oral desensitization procedure. The previously published desensitization protocols have either been performed in the intensive care unit, requiring significant cost and healthcare utilization, or have required a full-day outpatient commitment on behalf of the patient. OBJECTIVE To determine whether a multi-day outpatient oral clopidogrel desensitization protocol is effective and safe for patients with clopidogrel hypersensitivity. METHODS gWe retrospectively assessed the efficacy of a 10-dose outpatient multiday clopidogrel desensitization protocol performed in a university allergy-immunology center from April 2006 to October 2008 in patients with clopidogrel hypersensitivity. Patients were desensitized over 2–3 half-day clinical visits and were able to go home between desensitization sessions. A preliminary cost analysis was performed using the average of actual costs for the outpatient clopidogrel desensitization procedure and was compared with the average cost for an inpatient oral desensitization completed at our institution. RESULTS Eight patients with coronary artery disease, cardiac stent placement, and clopidogrel hypersensitivity underwent an outpatient multi-day oral clopidogrel desensitization procedure. All patients were successfully desensitized with the multi-day protocol without complications. No patient had recurrence of allergic reaction 3 months after the procedure. A preliminary cost analysis demonstrated a lower cost for the outpatient compared to the inpatient oral clopidogrel desensitization protocol. CONCLUSIONS This outpatient 10-dose multi-day clopidogrel desensitization protocol is a safe and effective novel approach for the treatment of clopidogrel hypersensitivity in patients with coronary artery disease and cardiac stent placement. In addition to safety and efficacy, this protocol offers the patient the convenience of avoiding hospital admission or full-day time commitments.

A retrospective analysis comparing subjects with isolated and coexistent vocal cord dysfunction and asthma.

Vocal cord dysfunction (VCD) is often misdiagnosed as asthma or complicates coexisting asthma. This study aimed to identify distinguishing clinical characteristics in patients with VCD, asthma, and coexisting VCD and asthma. We conducted a retrospective analysis of demographic and clinical data from 292 patients with VCD, asthma, coexisting VCD and asthma, and control subjects from an outpatient university asthma/allergy clinic. Concomitant asthma was present in 32.6% of VCD subjects. Overall, 42.4 % of all VCD subjects were previously misdiagnosed as having asthma for an average of 9.0 years. Upper airway symptoms were more prevalent in the VCD population and nocturnal apnea was more prevalent in comorbid VCD and asthma compared with either condition alone. Irritable bowel syndrome and chronic pain were identified as new comorbidities associated with VCD. VCD subjects who had been misdiagnosed with asthma had significantly more health care and asthma medication use compared to VCD subjects who had not mimicked asthma. There was no difference in asthma severity between those with and without VCD. Comorbid VCD and asthma led to an increase in long-acting β-agonist use only, but no difference in health care usage, compared with asthma alone. These findings suggest that the main morbidity associated with VCD may not lie in its inherent disease process, but instead in its ability to mimic asthma.

Outpatient aspirin desensitization for patients with aspirin hypersensitivity and cardiac disease.

BACKGROUND Cardiac disease is common and often treated with aspirin therapy. Patients who develop an immunoglobulin E (IgE) hypersensitivity reaction to aspirin must abort treatment and receive alternative antithrombotic agents. Aspirin desensitization is a therapeutic procedure that may allow patients with a history of hypersensitivity to safely resume aspirin treatment. A variety of inpatient desensitization protocols have been published for IgE-mediated reactions, but outpatient regimens have not been previously reported. OBJECTIVE We aimed to determine the efficacy and safety of a multiday outpatient aspirin desensitization protocol for patients with an IgE-mediated aspirin hypersensitivity. METHODS We retrospectively assessed the efficacy of a multidose aspirin desensitization protocol performed in a university allergy-immunology clinic between July 2006 and December 2009. Patients were referred for a diagnosis of aspirin hypersensitivity and required aspirin for cardiac disease treatment. The protocol involved 10 or 12 aspirin doses depending on the final dose of 81 or 325 mg. Patients were desensitized over 2 to 3 half-days and were able to return home in between desensitization sessions. RESULTS A total of 9 patients with cardiac disease and aspirin hypersensitivity underwent an outpatient multiday aspirin desensitization. Eight patients (89%) were successfully desensitized and 1 patient declined to continue with further desensitization. No adverse reactions requiring inpatient hospital care occurred during desensitization. CONCLUSIONS This novel outpatient multiday aspirin desensitization protocol was a safe and effective approach for the treatment of aspirin hypersensitivity in patients with cardiac disease who require aspirin therapy. This flexible protocol is convenient for patients by avoiding hospital admission and full-day time commitments.

Subcutaneous IgG replacement therapy is safe and well tolerated in lung transplant recipients.

Intravenous immunoglobulin (IVIG) replacement has been shown to decrease the risk of post-transplant infections secondary to hypogammaglobulinemia, however the use of subcutaneous immunoglobulin (SCIG) in this population has not been reported. A retrospective analysis of the efficacy and tolerability of subcutaneous immunoglobulin replacement on 10 lung-transplant recipients was performed. All 10 patients demonstrated an increase in IgG levels at three months that was sustained at 6-12 months with SCIG replacement therapy, with the majority (70%) tolerating infusion without complications. The results of this study suggest that subcutaneous IgG replacement therapy is a well tolerated alternative to IVIG.

Desensitization protocol for rituximab-induced serum sickness.

Rituximab, a chimeric anti-CD20 monoclonal antibody, is used to treat rheumatologic and hematologic diseases. Serum sickness, a Type III delayed hypersensitivity reaction, has been reported with rituximab treatment. Traditionally, drug desensitization has been used to treat Type I IgE-mediated hypersensitivity reactions. We report the first case of successful drug desensitization to rituximab in a patient with medication-induced serum sickness. In our case, a 37-year-old woman with Sjogrens syndrome and papillary thyroid carcinoma developed serum sickness 72 hours following rituximab infusion for gastric mucosal associated lymphoma tissue (MALT). Her MALT progressed after stopping rituximab. She underwent a rapid 12-step intravenous rituximab desensitization without recurrence of serum sickness. Following the completion of 4 rituximab desensitizations, she had gastric MALT remission. She received 25 maintenance rituximab doses using this desensitization protocol quarterly without complications. This is the first report documenting rituximab desensitization for the treatment of delayed drug reactions like serum sickness.

Vocal Cord Dysfunction and Asthma

Opinion StatementVocal cord dysfunction (VCD) is a functional disorder of the vocal cords characterized by exaggerated adduction of vocal cords during inspiration and/or expiration causing respiratory and laryngeal symptoms. VCD can exist in isolation and coexist with asthma, or it can mimic asthma. The missteps during the VCD and asthma diagnostic process and subsequent faulty clinical conclusions can lead to mistreatment and increased health care utilization that can last for years. Therefore, diagnostic precision in conjunction with optimal therapeutics is a prerequisite for the best patient outcomes in this patient population. An integrated approach is frequently required using multiple diagnostic modalities to make a correct diagnosis. The treatment options, usually applied in a step-wise progression, depend on the severity of presentation and the underlying type of VCD. Future studies should address the better identification of specific phenotypes of VCD and their corresponding treatments.