Canadian multidisciplinary expert consensus on the use of biologics in upper airways: a Delphi study.

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases. Knowledge gaps nevertheless exist in how best to approach patient care as a whole. There have been sixteen randomized, double-blind, placebo-controlled trails performed for CRSwNP targeted components of the Type 2 inflammatory pathway, notably interleukin (IL)-4, IL-5 and IL-13, IL- 5R, IL-33, and immunoglobulin (Ig)E. This white paper considers the perspectives of experts in various disciplines such as rhinology, allergy, and respirology across Canada, all of whom have unique and valuable insights to contribute on how to best approach patients with upper airway disease from a multidisciplinary perspective. METHODS: A Delphi Method process was utilized involving three rounds of questionnaires in which the first two were completed individually online and the third was discussed on a virtual platform with all the panelists. A national multidisciplinary expert panel of 34 certified specialists was created, composed of 16 rhinologists, 7 allergists, and 11 respirologists who evaluated the 20 original statements on a scale of 1-9 and provided comments. All ratings were quantitively reviewed by mean, median, mode, range, standard deviation and inter-rater reliability. Consensus was defined by relative interrater reliability measures-kappa coefficient ([Formula: see text]) value > 0.61. RESULTS: After three rounds, a total of 22 statements achieved consensus. This white paper only contains the final agreed upon statements and clear rationale and support for the statements regarding the use of biologics in patients with upper airway disease. CONCLUSION: This white paper provides guidance to Canadian physicians on the use of biologic therapy for the management of upper airway disease from a multidisciplinary perspective, but the medical and surgical regimen should ultimately be individualized to the patient. As more biologics become available and additional trials are published we will provide updated versions of this white paper every few years.

Defining Asthma-Chronic Obstructive Pulmonary Disease Overlap.

Much interest has been given to the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) in the past 2 decades, but the condition is still ill-defined. There is general agreement that a patient with longstanding asthma who develops fixed airflow obstruction after years of smoking has ACO although defining asthma in the face of COPD can be challenging. Many features of asthma are also found in patients with COPD without indicating an overlap and no consensus exists on which characteristics should be included in the definition of ACO. Nevertheless, some guidance has been issued to help clinicians and researchers to make a diagnosis of ACO and these will be reviewed here.

Asthma COPD overlap: Insights into cellular and molecular mechanisms.

Although there is still no consensus on the definition of Asthma-COPD Overlap (ACO), it is generally accepted that some patients with airway disease have features of both asthma and COPD. Just as its constituents, ACO consists of different phenotypes, possibly depending on the predominance of the underlying asthma or COPD-associated pathophysiological mechanisms. The clinical picture is influenced by the development of airway inflammatory processes either eosinophilic, neutrophilic or mixed, in addition to glandular changes leading to mucus hypersecretion and a variety of other airway structural changes. Although animal models have exposed how smoking-related changes can interact with those observed in asthma, much remains to be known about their interactions in humans and the additional modulating effects of environmental exposures. There is currently no solid evidence to establish the optimal treatment of ACO but it should understandably include an avoidance of environmental triggers such as smoking and relevant allergens. The recognition and targeting of "treatable traits" following phenotyping is a pragmatic approach to select the optimal pharmacological treatment for ACO, although an association of inhaled corticosteroids and bronchodilators is always required in these patients. This association acts both as an anti-inflammatory treatment for the asthma component and as a functional antagonist for the airway remodeling features. Research should be promoted on well phenotyped subgroups of ACO patients to determine their optimal management.

Exercise-Associated Dyspnea and Stridor: Thinking Beyond Asthma.

Breathlessness during sport can be caused by various cardiorespiratory conditions, but when associated with stridor, usually arises from an upper airway etiology. The term exercise-induced laryngeal obstruction (EILO) is now used to describe the phenomenon of transient glottic closure occurring in association with physical activity. Exercise-related laryngeal closure is most commonly encountered in athletic individuals and likely affects between 5% and 7% of all young adults and adolescents. The diagnosis of EILO is not always straightforward because features can overlap with exercise-induced asthma/exercise-induced bronchoconstriction. EILO can therefore remain misdiagnosed for years, and most patients receive inappropriate asthma therapy. In contrast with asthma, EILO symptoms are usually most prominent at maximal exercise intensity and resolve quickly on exercise cessation. It is important to recognize that EILO and asthma can coexist in a proportion of athletes. The criterion standard test for diagnosing EILO is continuous laryngoscopy during exercise testing, although eucapnic voluntary hyperpnea testing has also been used. Various surgical or pharmacological interventions can be used to treat EILO, but first-line treatment is breathing technique work. Further research is needed to establish the optimal treatment algorithm, and more work is needed to increase awareness of this important clinical entity.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations.

BACKGROUND AND OBJECTIVE: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. METHODS: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. RESULTS: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. CONCLUSION: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

A Distress Protocol for Respiratory Emergencies in Terminally Ill Patients With Lung Cancer or Chronic Obstructive Pulmonary Disease.

A combination of opioid, midazolam, and scopolamine (that we call "distress protocol" [DP]) is used to induce transient sedation when emergencies occur in palliative care. We wished to describe the prescription and administration of DP in terminally ill patients with either lung cancer or chronic obstructive pulmonary disease (COPD). In a retrospective study, 96 of 100 patients with cancer and 85 of 100 patients with COPD had a DP prescribed. Thirty patients with cancer and 29 with COPD received at least 1 DP. All patients receiving a DP for an appropriate indication were sedated within 30 minutes. There was no difference in survival from DP administration among patients who received it and those who did not.

Evaluation of Pulmonary Nodules Using the Spyglass Direct Visualization System Combined With Radial Endobronchial Ultrasound: A Clinical Feasibility Study.

BACKGROUND: Sampling of peripheral pulmonary nodules with radial endobronchial ultrasound (p-EBUS) increases diagnostic yield of bronchoscopy. However, diagnostic yield is influenced by numerous factors. OBJECTIVE: We evaluated the use of SpyGlass, a one millimeter diameter optic fiber, to obtain images of the distal mucosa and of pulmonary lesions detected with p-EBUS to determine if visual aspect of the distal mucosa was predictive of diagnosis. METHODS: We prospectively recruited subjects investigated for peripheral nodules. Bronchoscopy was performed and p-EBUS was used to locate the lesion through a guide sheath. The Spyglass fiber was introduced in the sheath to obtain images of the distal bronchial mucosa. Tissue sampling was subsequently done. RESULTS: Fifteen patients were enrolled in the study. A final diagnosis of malignancy was confirmed in 80%. All lesions could be located using p-EBUS (100%). Diagnostic sensitivity for p-EBUS was 58.3%. Distal mucosa could be imaged with SpyGlass in 14/15 patients (93.3%). Mucosal appearance was described as abnormal in 7 out of the 15 subjects. Mean SpyGlass procedure time was 6.5 minutes. No direct complication was reported. CONCLUSION: Spyglass can be used in combination with p-EBUS to obtain images of the distal bronchial mucosa and peripheral pulmonary nodules. More patients will be needed to confirm whether mucosal appearance can be predictive of malignancy.