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Vocal 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.

Background Allergen immunotherapy (AIT) is an effective treatment option for allergic rhinitis. Although conventional AIT takes 6 months to reach maintenance dosing, rush AIT accelerates the build-up period and reaches the maintenance dose months earlier. However, accelerated schedules of AIT carry an increased risk of systemic reactions (SR). Objective We aimed to describe a novel 1-day, eight-step modified environmental rush immunotherapy (MERIT) protocol, characteristics of the patients who underwent this therapy, and the safety of this procedure. We also compared distinguishing features of those patients with SRs. Methods We retrospectively analyzed demographic and clinical data of 362 adult patients seen in an outpatient university allergy clinic, from January 2005 to January 2015, and who underwent MERIT protocol treatment for allergic rhinitis. Results In a univariate analysis, the factors significantly associated with SR were lower body mass index (BMI); younger age; a higher number of allergens in the extracts; and the presence of cat, dust mite, and certain weed pollens. In a multivariate analysis, cat, dust mite, and mugwort were significantly associated with SRs. Over the 10-year period, 50 patients experienced SRs (13.81%), with a total number of 68 SRs. Only 4.7% of the SRs occurred on the MERIT day. Most SRs occurred >30 minutes and were mild. Our MERIT protocol continuation rate for all the patients was 49.2% and did not seem to be influenced by having an SR versus no SR. Conclusion We present a modified rush AIT protocol that seems to be effective and safe. Most patients tolerated therapy, and only a minority of patients developed SRs, which generally were mild. We identified novel risk factors for SRs that may help determine optimal dosing to decrease the risk of SRs. Ultimately, future studies will be needed to compare the safety of our MERIT protocol with traditional AIT.

Background. Immunosuppressive therapies have led to improved survival for lung transplant (LT) recipients but these therapies can lead to hypogammaglobulinemia (HGG) and potentially an increased risk of infection. Large prospective studies have not been performed to evaluate the impact of HGG on outcomes for LT recipients. Methods. This is a single-center prospective observational study of LT recipients. Pretransplant and posttransplant IgG levels were measured and related to infection, rejection, antibiotic use, and immunosuppression use. Results. One hundred thirty-three LT recipients were prospectively evaluated. Pretransplant IgG values were higher than IgG values at the time of transplant or any time thereafter (all P < 0.0001). Severe HGG (IgG < 400 mg/dL) was highest at the time of transplant (32.4%) while at 3, 6, 9, and 12 months posttransplant the prevalence of severe HGG was 7.4%, 7.5%, 8.9%, and 6.3%, respectively. Severe HGG was associated with 2 or more pneumonias (P = 0.0006) and increased number of antibiotic courses (P = 0.003) compared with the subjects without severe HGG. Pretransplant IgG level and less than 30% of pretransplant protective pneumococcal antibody levels were identified as pretransplant risk factors for severe HGG. In multivariate analysis, chronic obstructive pulmonary disease as the underlying disease and the use of basiliximab as the induction agent in conjunction with higher prednisone and mycophenolate dosing were most predictive of severe HGG (P = 0.005), whereas the combination of age, severe HGG and number of acute steroid courses were most predictive of total days of pneumonia (P = 0.0001). Conclusions. Our large prospective study identifies risk factors for severe HGG after LT and demonstrates that LT recipients with severe HGG are at increased risk for recurrent pneumonias and more antibiotic courses.

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.

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.

Despite its prevalence and cost to the healthcare system, the pathogenesis of asthma remains poorly understood. It is clear that asthma is a heterogeneous disease and recent approaches have attempted to define asthma subgroups based on inflammatory phenotypes. Characteristics of the cellular makeup of sputum, blood, bronchoalveolar lavage fluid, and endobronchial biopsies have been examined in asthmatic subjects, with a primary focus on eosinophils and neutrophils, and, more recently, mast cells. The inflammatory phenotypes identified to date include eosinophilic asthma, neutrophilic asthma, pauci-granulocytic asthma, and T helper 2-associated asthma. Defining these phenotypes has already led to more personalized and successful targeted therapies, with new developments on the horizon.

Background Food oral immunotherapy (OIT) is a promising but still investigational new therapy for food allergy. Objective We sought to investigate beliefs and opinions among OIT participants and nonparticipants to better understand community awareness of this therapy. Methods A 30-question on-line survey was administered to members, website visitors, and social media followers of the Kids with Food Allergy Foundation. Questions inquired about general knowledge and attitudes about OIT, its reported safety and efficacy, complications, insurance coverage, and its Food and Drug Administration (FDA) approval status. Results Among 1,274 survey respondents, 15.9% had discussed OIT as a treatment option with their allergy provider. Five percent ( n = 64) of respondents reported that their child was currently participating in OIT, including 73.4% ( n = 47) in a private practice setting. Participants reported varying degrees of being informed about OIT safety (85%), efficacy (46.4% told unrestricted ingestion), risks (relapse 53.4%, eosinophilic esophagitis 3.5%, oral allergy syndrome 10.7%, and failure 56.9%). Significantly fewer participants than nonparticipants agreed that OIT's present safety, efficacy, risks, and approval status would dissuade participation. Significantly fewer participants agreed that OIT should not be offered outside the research setting without definitive proof of both its safety and efficacy. Conclusion In this exploratory study, differences in beliefs and opinions existed between OIT participants and nonparticipants. Among participants, there were also significant differences in beliefs among academic versus nonacademic participants. Accurate and complete information about OIT safety, efficacy, risks, and approval status was not universally conveyed.

Arthritis is among the leading causes of disability in the developed world. There remains no cure for this disease and the current treatments are only modestly effective at slowing the disease's progression and providing symptomatic relief. The clinical effectiveness of current treatment regimens has been limited by short half-lives of the drugs and the requirement for repeated systemic administration. Utilizing gene transfer approaches for the treatment of arthritis may overcome some of the obstacles associated with current treatment strategies. The present review examines recent developments in gene therapy for arthritis. Delivery strategies, gene transfer vectors, candidate genes, and safety are also discussed.

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.