Prevalence of Anxiety as a Variable in Treatment Outcomes for Individuals With Chronic Refractory Cough.

PURPOSE: Anxiety is a mental state characterized by an intense sense of tension, worry, or apprehension relative to something adverse that might happen in the future. Anxiety is a known comorbidity in cough patients, yet its prevalence among those with chronic refractory cough (CRC) is unknown. Anxiety is not typically assessed during evaluation for CRC, but treatments for CRC such as neuromodulators and behavioral cough suppression therapy (BCST) may potentially attenuate anxiety. This preliminary study investigates the potential prevalence of anxiety in CRC and its possible role in treatment outcomes. METHOD: CRC patients seen in a specialty clinic at the University of Utah or the University of Montana completed the Leicester Cough Questionnaire (LCQ) pre- and post-BCST treatment. Participants were dichotomized into positive anxiety screen (PAS) and negative anxiety screen (NAS) groups based on presence or absence of documented anxiety within electronic medical records at the University of Utah and based on a Generalized Anxiety Disorder-7 score > 5 at the University of Montana. RESULTS: Of the 86 total participants, 37 (43%) were in the PAS group (29 females, Mage = 56 ± 13) and 49 (57%) were in the NAS group (36 females, Mage = 64 ± 14). Eighty-nine percent of CRC participants with a PAS reported a clinically meaningful improvement in LCQ total score following treatment compared to 65% of NAS participants. Furthermore, mean pre- to posttreatment change scores on the LCQ were significantly greater within the PAS group (p = .002, Cohen's d = 0.7, indicating a moderate to large effect size). CONCLUSION: This preliminary study suggests that (a) anxiety may be prevalent among those with CRC and (b) those patients who screen positive for anxiety report greater benefit from BCST.

Factors influencing behavioral cough suppression therapy in children with nonspecific chronic cough.

BACKGROUND: Behavioral cough suppression therapy (BCST) with a speech-language pathologist is a common treatment for chronic nonspecific cough (a.k.a., tic cough) in children. Yet, the outcomes and duration of pediatric BCST have eluded formal investigation. This study examined whether BCST improves cough in children with nonspecific cough and factors that predict the course of treatment. Additionally, the cough characteristics and comorbidities associated with the condition were examined. METHODS: A retrospective, observational cohort design was utilized. Cough characteristics, medical history, and BCST treatment details and outcomes for 151 children were extracted from the electronic medical record of a large outpatient pediatric otolaryngology clinic. RESULTS: Cough was dry and onset unaccompanied by illness in most cases. Roughly half of patients reported gradual onset and cough proceeded by tickle. On average, patients experienced symptoms for 19 months (SD = 20.09) before diagnosis. Rates of comorbid General Anxiety Disorder were elevated compared to pediatric norms. Additionally, high rates of asthma (22.1%), reflux (62.3%), and disordered sleep breathing (19.2%) were observed. Common findings on laryngoscopy included interarytenoid edema and erythema. Vocal fold changes were observed in 22.9% of children. BCST reduced cough in 92.5% of patients following an average of 1.7 sessions. Comorbid behavioral health diagnoses (p = 0.013) or induced laryngeal obstruction symptoms (p = 0.025) were significant predictors of increased therapy sessions. Cough proceeded by tickle significantly predicted fewer sessions in therapy (p = 0.011). INTERPRETATION: Although randomized clinical trials are needed, these data suggest that BCST is a low-risk, effective treatment for children with nonspecific cough.

Normative Values for the Leicester Cough Questionnaire in Healthy Individuals.

INTRODUCTION: The primary self-assessment questionnaire used for patients with chronic cough is the Leicester Cough Questionnaire (LCQ). The LCQ is a validated questionnaire that ranges in total score from 3 to 21. While it is known that a higher score on the LCQ reflects a better quality of life, normative data have not been reported for this questionnaire. OBJECTIVE: The purpose of this study was to determine normative LCQ scores on a healthy population without cough. METHODS: The LCQ was distributed via electronic survey to the authors' universities, professional affiliation email lists, and personal contacts. Participants were included if they were at least 18, nonsmokers, and without abnormal cough, without pulmonary disease, and without neurological disease. Participants answered questions regarding age, gender, and race/ethnicity, and completed the 19 LCQ questions. RESULTS: One hundred forty-three (118 women) LCQ responses were analyzed. Average participant age was 47 years (SD = 13) and 133 (93%) were Caucasian. The mean LCQ Total score was 20.23 (SD = 0.85) with scores ranging from 17.05 to 21. CONCLUSIONS: This study determined the following LCQ scores should be considered normal threshold scores: Total score - 17.68, Physical domain - 5.36, Psychological domain - 5.81, and Social domain - 6.06. The findings of this study will assist clinicians in determining severity of cough impact on quality of life using the LCQ. Further research is needed to ensure more complete participant demographic representation.

Effect of Behavioral Cough Suppression Therapy Delivered via Telehealth.

OBJECTIVES/HYPOTHESIS: Behavioral cough suppression therapy (BCST) has demonstrated up to 88% effectiveness at treating refractory chronic cough (RCC). With onset of the COVID-19 pandemic, along with many other medical services, BCST shifted to telehealth delivery. Our group hypothesized that BCST delivered via telemedicine by a specialized Speech-Language Pathologist would be comparable to previously reported response to treatment for in-person settings. STUDY DESIGN: Retrospective review. METHODS: An Emory IRB approved, retrospective review of electronic medical records was completed for RCC patients who received BCST via telehealth from March 2020 through January 2022 at Emory Voice Center. Patients were included in the study if they had a diagnosis of RCC, were referred for BCST, were seen for at least one therapy session in the telehealth setting, and provided Cough Severity Index (CSI) data pre and post-treatment. Patients were excluded if they had incomplete datasets, a known pulmonary condition, structural laryngeal disorders, smoking history, dysphagia, and ACE-inhibitor use. Change in CSI score pre- and post-treatment was calculated to determine treatment effect. Paired-samples t-tests were conducted to compare pre-and post-treatment CSI score change. RESULTS: Fifty-one RCC patients were included in this study; 88% were female with an average age of 60 years (SD = 12.68). Post-treatment CSI scores were significantly lower than pretreatment CSI scores (P < 0.0001). These findings are comparable to historical documented CSI change achieved with in-person BCST. CONCLUSIONS: This study provides preliminary evidence of the efficacy of BCST via telehealth for treating RCC. The findings of this study support the continued flexibility in speech-language pathology service delivery to include in-person and telehealth platforms for RCC beyond the COVID-19 pandemic.

Patient-Reported Qualitative Analysis of Chronic Refractory Cough.

PURPOSE: Chronic cough has been shown to be associated with adverse effects on quality of life. There is a paucity of research characterizing quality-of-life factors associated with chronic refractory cough (CRC), a cough persisting > 8 weeks despite evaluation and treatment of possible etiologies. The purpose of this study was to elucidate the features of CRC from the patient's perspective, including presenting symptoms, past treatment methods, and quality-of-life factors. METHOD: Prospective semistructured interviews were conducted, recorded, and transcribed for 20 patients diagnosed with CRC. Exclusion criteria included lung disease, smoking history, laryngeal cancer, and neurological disease. Grounded theory analysis was completed on transcribed interviews. RESULTS: Eighteen participants were women. Mean participant age was 53.5 years (SD = 1.41), and average cough duration was 52 months (SD = 71.6 months). Responses to 30 open-ended questions revealed four dominant themes with 24 subthemes. CONCLUSIONS: CRC affects patient quality of life. Understanding patient perspective on CRC diagnosis and treatment helps providers better understand the physical and emotional toll CRC takes on patients. Findings suggest that providers should spend more time counseling patients regarding their treatment and diagnosis, as patients with CRC do not always fully understand their diagnosis and resort to self-blame.

Long-Term Treatment Outcomes after Behavioral Speech Therapy for Chronic Refractory Cough.

INTRODUCTION: Current literature reveals that up to 88% of individuals undergoing behavioral speech therapy (BST) for chronic refractory cough (CRC) demonstrate benefit at 4-8 weeks post-treatment. However, investigations of BST are confounded by overlapping use of neuromodulators, missing follow-up data, and an absence of long-term outcomes. This study investigated treatment outcomes beyond 6 months in individuals diagnosed with CRC, and whose treatment outcomes were clinically undocumented. METHODS: Participants with CRC 6 months or greater beyond treatment completion were recruited. Participants completed a post-treatment Leicester Cough Questionnaire (LCQ) and a telephone interview. Demographic data, cough characteristics, treatment adherence, BST outcomes, and pre- and post-treatment LCQ scores were evaluated. RESULTS: 80 individuals met inclusion criteria and 29 consented to participate. Of these, 27 were recommended BST. The majority were female (19/27) with average age of 58 years (SD = 12). Mean cough duration was 60 months (SD = 98) and mean post-BST duration was 20 months (SD = 9). A significant increase in pre- to post-treatment LCQ scores occurred [4.4 (SD = 4.2)] (p < 0.0001). CONCLUSION: This study addressed long-term BST benefit for CRC and demonstrated a significant improvement in long-term post-treatment LCQ total scores more than a year after BST for CRC. More than half of participants indicated improvement or elimination of their cough. These findings further support the benefit of BST for CRC. Future research should consider patient perspectives about treatment outcomes given that 44% of participants reported no benefit from BST.

Design, Synthesis and Characterization of Covalent KDM5 Inhibitors.

Histone lysine demethylases (KDMs) are involved in the dynamic regulation of gene expression and they play a critical role in several biological processes. Achieving selectivity over the different KDMs has been a major challenge for KDM inhibitor development. Here we report potent and selective KDM5 covalent inhibitors designed to target cysteine residues only present in the KDM5 sub-family. The covalent binding to the targeted proteins was confirmed by MS and time-dependent inhibition. Additional competition assays show that compounds were non 2-OG competitive. Target engagement and ChIP-seq analysis showed that the compounds inhibited the KDM5 members in cells at nano- to micromolar levels and induce a global increase of the H3K4me3 mark at transcriptional start sites.

Bench-Stable Transfer Reagent Facilitates the Generation of Trifluoromethyl-sulfonimidamides.

Sulfonimidamides are an emerging bioisosteric replacement in medicinal chemistry projects, and therefore new chemistries are necessary to access this functionality. The general synthesis of CF3-sulfonimidamides from an activated bench-stable transfer reagent is described. A diverse reaction scope is demonstrated, with a wide range of nucleophilic amines being tolerated in this transformation. The CF3-sulfonimidamides obtained contain an additional diversity point, in the form a protected imine, that could be unmasked to allow late stage modifications.

Feline gastrointestinal eosinophilic sclerosing fibroplasia: 13 cases and review of an emerging clinical entity.

OBJECTIVE: Feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF) is a recently described inflammatory disease of cats affecting stomach or intestines and draining regional lymph nodes. This study presents clinical and laboratory data on 13 newly described cases from Australia (11) and the UK (two). OBSERVATIONS: The disease was most often observed in middle-aged cats (median 7 years of age; interquartile range 5-9 years). Ragdolls (7/13) and males (9/13) were overrepresented. Cats generally had a long history of vomiting and/or diarrhoea. Lesions were typically large, hard, non-painful, easily palpable and most commonly situated near the pylorus or ileocaecocolic junction. Lesions were heterogeneous ultrasonographically and on sectioning at celiotomy or necropsy. Masses were hard and 'gritty' on fine-needle aspiration due to internal trabeculae made up of mature collagen bundles. Bacteria were commonly detected within masses (9/13 cases) using either culture or conventional light microscopy and a panel of special stains, and/or fluorescence in situ hybridisation (FISH), although detection often required a diligent search of multiple tissue sections. A consistent bacterial morphology could not be appreciated among the different cases. OUTCOME: Patients were treated with a variable combination of cytoreduction (debulking and biopsy, to complete surgical resection), immunosuppressive therapy and antimicrobial agents. Many cats had a poor outcome, which was attributable to late diagnosis combined with suboptimal management. It is hoped that suggestions outlined in the discussion may improve clinical outcomes and long-term survival in future cases.