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BACKGROUND: Pulmonary hypertension (PH) accompanying COPD (PH-COPD) is associated with worse outcomes than COPD alone. There are currently no approved therapies to treat PH-COPD. The PERFECT study (ClinicalTrials.gov: NCT03496623) evaluated the safety and efficacy of inhaled treprostinil (iTRE) in this patient population. METHODS: Patients with PH-COPD (mean pulmonary arterial pressure ≥30â mmHg and pulmonary vascular resistance ≥4â WU) were enrolled in a multicentre, randomised (1:1), double-blind, placebo-controlled, 12-week, crossover study. A contingent parallel design was also prespecified and implemented, based on a blinded interim analysis of missing data. Patients received treatment with iTRE up to 12 breaths (72â µg) 4 times daily or placebo. The primary efficacy end-point was change in peak 6-min walk distance (6MWD) at week 12. RESULTS: In total, 76 patients were randomised, 64 in the original crossover design and 12 in the contingent parallel design; 66 patients received iTRE and 58 received placebo. The study was terminated early at the recommendation of the data and safety monitoring committee based on the totality of evidence that iTRE increased the risk of serious adverse events and suggestive evidence of an increased risk of mortality. The change in 6MWD was numerically worse with iTRE exposure than with placebo exposure. CONCLUSIONS: The risk-benefit observations associated with iTRE in patients with PH-COPD did not support continuation of the PERFECT study. The results of this study do not support iTRE as a viable treatment option in patients with PH-COPD.
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Antihipertensivos , Estudios Cruzados , Epoprostenol , Hipertensión Pulmonar , Enfermedad Pulmonar Obstructiva Crónica , Prueba de Paso , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Epoprostenol/análogos & derivados , Epoprostenol/administración & dosificación , Epoprostenol/uso terapéutico , Femenino , Masculino , Hipertensión Pulmonar/tratamiento farmacológico , Administración por Inhalación , Anciano , Persona de Mediana Edad , Método Doble Ciego , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: The Nasal Obstruction Symptom Evaluation (NOSE)-Perf scale was developed and validated to measure symptoms associated with nasal septal perforations. This study reports the application of the NOSE-Perf scale to evaluate symptom change following septal perforation repair. METHODS: Patients with NOSE-Perf evaluations ≥6 months following attempted perforation closure from July 2018 to December 2021 utilizing bilateral nasal mucosal flaps with an interposition graft were eligible for study inclusion. Change in NOSE-Perf scores were noted. Patient demographics, perforation size, and concurrent functional procedures were analyzed for impact on symptom outcomes. RESULTS: One-hundred and seventeen patients met the study criteria. Seventy-nine (67.5%) of the patients were female and the mean (range) age at surgery was 47.3 (14-78) years. Repair failure was noted in 7 (6.0%) patients. Mean (SD) preoperative NOSE-Perf score was 25.3 (95% CI, 23.5-27.1) and postoperative score was 7.9 (95% CI, 6.5-9.3). Minimal clinically important difference (MCID) was estimated and greater than 91% of patients had improvement above this threshold. Patient age, perforation size, or concurrent functional procedures did not impact outcomes. Postoperative scores at short (2-4 months), intermediate (5-8 months), and long-term (≥9 months) time periods showed significant improvement (all p < 0.001) compared to preoperative NOSE-Perf scores. CONCLUSION: Significant reduction in nasal symptoms as measured by the NOSE-Perf scale is noted following bilateral mucosal flap repair. Although the nose does not completely normalize following repair, clinically important improvement was noted in at least 91% of patients. The NOSE-Perf scale is positioned to play a role in the standardization of septal perforation evaluation and outcomes assessment. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3067-3072, 2024.
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Perforación del Tabique Nasal , Colgajos Quirúrgicos , Humanos , Perforación del Tabique Nasal/cirugía , Femenino , Masculino , Adulto , Persona de Mediana Edad , Anciano , Adolescente , Adulto Joven , Colgajos Quirúrgicos/efectos adversos , Obstrucción Nasal/cirugía , Obstrucción Nasal/etiología , Resultado del Tratamiento , Evaluación de Síntomas/métodos , Mucosa Nasal/lesiones , Tabique Nasal/cirugíaRESUMEN
BACKGROUND: Nasal septal perforations (NSP) can have a heterogeneous appearance on endoscopic examination with varying degrees of crusting, inflammatory change, and associated septal deviation. The clinical applicability of these findings as contributors to patient symptoms may be enhanced by use of a standardized assessment. METHODS: Video nasal endoscopy recordings were obtained from 40 patients with NSP. Five raters with varied levels of training ranging from a senior resident to an experienced septal perforation surgeon independently reviewed the videos for the following exam findings: crusting, scarring, granulation tissue, septal deviation, and edema. Scoring for each item was reported on a 3-point (0-2) scale, and each reviewer repeated scoring at a 14-day interval. Interrater and intrarater agreement were calculated using Fleiss kappa for each item and the total scores. Additionally, endoscopy scores were correlated with patient-reported NOSE-Perf symptom scores. RESULTS: Interrater agreement for the overall instrument was in the "fair-to-moderate" range with the following interrater agreement for each item: crusting (0.458-0.575), scarring (0.286-0.308), granulation (0.403-0.406), deviation (0.487-0.494), and edema (0.253-0.406). Intrarater agreement was generally "substantial" for individual items as well as the overall instrument (0.688). The NSP endoscopy scores were moderately correlated with NOSE-Perf scores (r = 0.44, p = 0.008). CONCLUSIONS: An endoscopic evaluation of NSP comprising five exam findings has acceptable interrater and intrarater reliability and correlates with patient-reported outcomes. NSP endoscopy may be applied to future clinical studies for characterization of NSP and assessment of treatment outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3049-3053, 2024.
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Endoscopía , Perforación del Tabique Nasal , Grabación en Video , Humanos , Perforación del Tabique Nasal/diagnóstico , Endoscopía/métodos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Anciano , Tabique Nasal , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To describe and illustrate septal perforation shape through the documentation and analysis of length and height measurements. A secondary objective is to correlate perforation size to surgical and nonsurgical etiologies. STUY DESIGN: Retrospective case series. SETTING: Tertiary academic medical center. METHODS: Length and height of consecutively treated perforations over a 3-year period were measured directly or through computed tomography. Mean differences in length and height measurements were compared and regression analysis used to determine perforation shape and the effect of etiology on perforation size. Perforations were classified by length into small (1-5 mm), medium (6-15 mm), and large (>15 mm) and correlated to shape and etiology. RESULTS: One hundred twenty-four patients (mean age 50.4 years, 60.5% female) met study inclusion criteria. Height was less than length in 93% of perforations 5 mm or greater in length. Mean perforation height was significantly less than length for medium and large perforations (P < .001). Mean length and height measurements of nonsurgical perforations were greater than those for surgical perforations (P < .001). CONCLUSION: Height is less than length in over 90% of septal perforations. Most perforations assume an elliptical shape as they enlarge. Accurate measurement and presentation of length and height is relevant information to perforation management decisions and for the evaluation of treatment outcomes.
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OBJECTIVE: To perform the translation, cultural adaptation, and validation of the NOSE-Perf Scale to Brazilian Portuguese. METHODS: This study was divided into two stages. In the first stage, the questionnaire was submitted for translation and cultural adaptation, following the guidelines recommended by the ISPOR Task Force (International Society for Pharmacoeconomics and Outcomes Research). Then, the Brazilian Portuguese version of the NOSE-Perf scale was applied to a group with septal perforation and a control group. The group with perforation answered the questionnaire again after one month. Internal consistency, test-retest reliability, and discriminant validity were assessed. RESULTS: The Brazilian Portuguese version of the NOSE-Perf scale was applied to 32 participants, 16 from the group with septal perforations and 16 controls. The instrument obtained high internal consistency, with Cronbach's alpha scores of 0.986. High reliability was also obtained, with Spearman's correlation coefficient of 0.996 (pâ¯<â¯0.001) and the intraclass correlation coefficient of 0.965 with a 95% Confidence Interval (95% CI) of 0.886â0.988. The NSP group obtained a mean total score of 13.8⯱â¯12.6 and the control group a score of 2.3⯱â¯1.8, with a statistical difference between the groups (pâ¯<â¯0.001), demonstrating good discriminant validity. CONCLUSION: The Brazilian Portuguese version of the NOSE-Perf scale is a reliable and valid instrument for measuring symptoms in patients with nasal septum perforations. LEVEL OF EVIDENCE: Level 2-Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence.
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OBJECTIVE: Critical components of the nasal endoscopic examination have not been definitively established for either the normal examination or for clinical disorders. This study aimed to identify concordance among rhinologists regarding the importance of examination findings for various nasal pathologies. STUDY DESIGN: A consortium of 19 expert rhinologists across the United States was asked to rank the importance of findings on nasal endoscopy for 5 different sinonasal symptom presentations. SETTING: An online questionnaire was distributed in July 2023. METHODS: The questionnaire utilized JotForm® software and featured 5 cases with a set of 4 identical questions per case, each covering a common indication for nasal endoscopy. Rankings were synthesized into Normalized Attention Scores (NASs) and Weighted Normalized Attention Scores (W-NASs) to represent the perceived importance of each feature, scaled from 0 to 1. RESULTS: General concordance was found for examination findings on nasal endoscopy within each case. The perceived features of importance differed between cases based on clinical presentation. For instance, in evaluating postnasal drip, the middle meatus was selected as the most important structure to examine (NAS, 0.73), with mucus selected as the most important abnormal finding (W-NAS, 0.66). The primary feature of interest for mucus was whether it was purulent or not (W-NAS, 0.67). Similar analyses were performed for features in each case. CONCLUSION: The implicit framework existing among rhinologists may help standardize examinations and improve diagnostic accuracy, augment the instruction of trainees, and inform the development of artificially intelligent algorithms to enhance clinical decision-making during nasal endoscopy.
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Background: Unlike acute rhinosinusitis (ARS) which is mostly viral in etiology, the role of viruses in chronic rhinosinusitis (CRS) remains unclear. Viruses may play a role in initiation, exacerbations or perpetuate chronic inflammatory responses in the sinonasal mucosa. Research needs to characterize whether viruses are part of the normal sinonasal microbiome, colonizers or pathogenic. Methods: Systematic review of the English literature was conducted. Following databases were searched with an initial search conducted in November 2021 and then updated through June 2023: Ovid Medline (1946 to present), Ovid Embase (1988 to present), Scopus (2004 to present) and Web of Science (1975 to present). MeSH (Medical Subject Headings) terms included: viruses, virus diseases, sinusitis, and rhinovirus. Keywords: virus, viral infection*, sinusitis, rhinovirus, chronic rhinosinusitis, CRS, respiratory virus, respiratory infection*, and exacerbat*. A supplementary search was conducted through September 2023: Ovid Medline (1946 to present), Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) Daily. Keywords used were: virus, viral infection*, sinusitis, chronic rhinosinusitis, CRS, respiratory virus, respiratory infection*, and exacerbat*. Results: Thirty studies on viruses in CRS met inclusion criteria for full review. These included 17 studies on prevalence of virus in CRS, 5 examining probable causes of host susceptibility to viral infections in CRS, and 8 studies examining pathological pathways in viral association of CRS. The prevalence of viruses in nasal specimens of CRS subjects was higher as compared to controls in most studies, though a few studies showed otherwise. Rhinovirus was the most common virus detected. Studies showed that viruses may be associated with persistent hyper-responsiveness in the sinonasal mucosa, susceptibility to bacterial infections, upregulation of genes involved in the immune response and airway remodeling as well as CRS exacerbations. Presence of viruses was also associated with worse symptom severity scores in CRS subjects. Conclusion: Most data show higher presence of viruses in nasal and serum samples of CRS subjects as compared to controls but their exact role in CRS pathophysiology in unclear. Large studies with longitudinal sampling at all disease phases (i.e., prior to disease initiation, during disease initiation, during disease persistence, and during exacerbations) using standardized sampling techniques are needed to definitively elucidate the role of virus in CRS.
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Inteligencia Artificial , Telemedicina , Humanos , Enfermedad Crónica , Rinitis/diagnóstico , Femenino , Masculino , Adulto , Persona de Mediana EdadRESUMEN
Abstract Introduction Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and positive sinonasal bacterial cultures may be recalcitrant to topical therapy alone due to the additional local inflammatory burden associated with bacterial infection/colonization. Objectives To evaluate sinonasal outcomes in CRSwNP patients with a positive perioperative bacterial culture, who were treated with postoperative intranasal corticosteroids (INCS) alone versus INCS in combination with a short-term course of oral corticosteroids (OCS). Methods This is a retrospective chart review of CRSwNP patients. A total of 59 patients met inclusion criteria, including positive perioperative bacterial culture and treatment with INCS with or without concomitant use of OCS. Two cohorts were formed based on the chosen postoperative medical treatment; 32 patients underwent postoperative INCS alone, while 27 underwent INCS plus a ≤ 2-week course of OCS. The 22-item sinonasal outcome test (SNOT-22) scores and Lund-Kennedy scores (LKS) were assessed preoperatively, and at 2-week, 4-week, and 4 to 6 months after endoscopic sinus surgery (ESS). Results There were no statistically significant differences in postoperative sinonasal symptoms or endoscopic scores between the cohorts treated with INCS plus OCS versus those prescribed INCS alone (p > 0.05). Our regression model failed to demonstrate a relationship between the use of OCS and better sinonasal outcomes at 2-week, 4-week, and 4 to 6 months after ESS (p > 0.05). Conclusions Our study suggests that in a cohort of CRSwNP patients with recent bacterial infections, the postoperative use of combined OCS and INCS did not result in a statistical improvement of endoscopic and symptomatic outcomes over INCS irrigation alone. However, both treatment groups had a clinically significant improvement based on the Minimal Clinically Important Difference.