Impact of chronic obstructive pulmonary disease on mortality: A large national cohort study.

BACKGROUND AND OBJECTIVE: The global burden of chronic obstructive pulmonary disease (COPD) is increasing and COPD patients are at higher risk for all-cause mortality. We aimed to evaluate the impact of COPD on specific-cause mortality using national data. METHODS: This was nationwide retrospective cohort study of 340, 767 adults aged 40-84 years who lacked COPD diagnosis at baseline between 1 January 2003 and 31 December 2013. Incident COPD was defined by reference to COPD claim codes and prescription of COPD medication at least twice annually. Cox proportional hazard ratio (HR) for each cause of death in the COPD group was compared to that of the non-COPD group, with other causes of death accounted as the competing risk. RESULTS: All-cause mortality was higher in the COPD (2,978 per 100, 000 person-years) than the non-COPD group (629 per 100, 000 person-years) and adjusted HR was 1.41 (95% CI = 1.32, 1.50). The association was particularly strong for chronic lower airway disease (adjusted sub-HR = 9.67; 95% CI = 7.21, 12.96) and lung cancer (adjusted sub-HR = 3.16; 95% CI = 2.68, 3.71), and the association was stronger in those aged <60 years. CONCLUSION: In this large national cohort, COPD patients were at a statistically significant higher risk for all-cause mortality than those without COPD. They were more likely to die from chronic lower airway disease, lung cancer and pneumonia than subjects without COPD. The impact of COPD on specific mortalities was stronger in younger subjects.

Sustained control of recalcitrant chronic spontaneous urticaria after initiation of inflammatory airway diseases treatment: two case reports.

BACKGROUND: Current classification of chronic urticaria is primarily based on clinical presentation of skin manifestations. Hence, therapeutic treatment is primarily aimed locally for immediate symptom relief. We reason that limiting therapeutic strategies to the skin pathology might be inadequate since cellular activation and inflammation might be triggered remotely. CASE PRESENTATION: In this series two patients had exhausted all current treatments for recalcitrant urticaria but remained symptomatic. The first case was 26-year-old Caucasian female and the second was 63-year-old African American female. Both cases had frequent breakthrough urticaria requiring frequent pulsating courses of prednisone to control urticaria despite treatment with omalizumab and antihistamines. When inflammatory airway disease was discovered and managed with inhaled corticosteroid, urticaria is controlled much faster without the need of high dose immunosuppression over several years of observation. Coincidentally, autoimmune thyroiditis and anti-immunogobulin-E immunoglobulin-G titers dropped significantly in one case with sustained inhaled corticosteroid therapy. CONCLUSIONS: We suggest a novel approach of controlling remote epithelial site inflammation in these two cases that resulted in sustained-control of urticaria symptoms without the need for systemic corticosteroids or immunosuppressant. The changes of autoimmune antibodies might be the consequences of tolerance breaking from chronic lower airway inflammation as observed in other epithelial inflammatory condition like in celiac disease and rheumatoid arthritis.

Salbutamol transport and deposition in healthy cat airways under different breathing conditions and particle sizes.

Salbutamol is a bronchodilatator commonly used for the treatment of feline inflammatory lower airway disease, including asthma or acute bronchospasm. As in humans, a pressurized metered dose inhaler (pMDI) is used in conjunction with a spacer and a spherical mask to facilitate salbutamol administration. However, efficacy of inhalation therapy is influenced by different factors including the non-cooperative character of cats. In this study, the goal was to use computational fluid dynamics (CFD) to analyze the impact of breathing patterns and salbutamol particle size on overall drug transport and deposition using a specific spherical mask and spacer designed for cats. A model incorporating three-dimensional cat airway geometry, a commercially available spherical mask, and a 10 cm spacer, was used for CFD analysis. Two peak inspiratory flows were tested: 30 mL/s and 126 mL/s. Simulations were performed with 30s breathing different inspiratory and expiratory times, respiratory frequencies and peaks. Droplet spray transport and deposition were simulated with different particle sizes typical of the drug delivery therapies (1, 5, 10, and 15 µm). The percentage of particle deposition into the device and upper airways decreased with increasing particle diameter during both flows imposed in this cat model. During increased mean ventilatory rate (MVR) conditions, most of the salbutamol was lost in the upper airways. And during decreased MVR conditions, most of the particles remained in suspension (still in hold-up) between the mask and the carina, indicating the need for more than 30 s to be transported. In both flows the percentage of particles traveling to the lung was low at 1.5%-2.3%. In conclusion, in contrast to what has been described in the human literature, the results from this feline model suggest that the percentage of particles deposited on the upper airway decreases with increasing particle diameter.

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.

The Role of IgE in Upper and Lower Airway Disease: More Than Just Allergy!

Immunoglobulin E (IgE) is a well-known key factor in allergic airway disease; however, its central role in non-allergic airway inflammation is often underestimated. In some airway diseases, IgE is produced as a result of allergic sensitization. However, in others, IgE production occurs despite the lack of a specific allergen. Although multiple pathways contribute to the production of IgE in airway disease, it is its activity in mediating the inflammatory response that is associated with disease. Therefore, an understanding of IgE as the unifying component of upper and lower airway diseases has important implications for both diagnosis and treatment. Understanding the role of IgE in each upper and lower airway disease highlights its potential utility as a diagnostic marker and therapeutic target. Further classification of these diseases by whether they are IgE mediated or non-IgE mediated, rather than by the existence of an underlying allergic component, accounts for both systemic and localized IgE activity. Improvements in diagnostic methodologies and standardization of clinical practices with this classification in mind can help identify patients with IgE-mediated diseases. In doing so, this group of patients can receive optimal care through targeted anti-IgE therapeutics, which have already demonstrated efficacy across numerous IgE-mediated upper and lower airway diseases.

Pemphigoid of the pulmonary system (POPS): A review of a less recognized feature.

This review of Pemphigoid of the Pulmonary System (POPS) is a comprehensive description of pulmonary involvement in patients with mucous membrane pemphigoid (MMP), which is an orphan autoimmune blistering disease. The objective of the review was to analyze clinical features of pulmonary involvement in MMP. This POPS review is a case series in which multiple search engines were utilized from inception to June 2022 for cases of MMP with biopsy and immunopathology proven tracheal and bronchial pemphigoid. Clinical profiles prior to pulmonary involvement, bronchoscopy findings, clinical course and therapy were recorded and cause of death was analyzed. Patients with documented MMP who developed tracheal, bronchial and pulmonary involvement were included in the POPS review. Histology and immunopathology documentation were essential diagnostic criteria. Comparison groups were not possible. Patients were treated with immunosuppressive therapy. Some required surgical interventions. Six of the 11 patients attained complete or partial remission on or off therapy. Five patients died from pulmonary complications. The POPS review had six females and five males. The mean age at onset was 20 years (range 4-76), while 80% of the patients were under 40 years. All had severe widespread MMP involving three to five mucosal tissues. 100% had oral, 82% had ocular and cutaneous involvement. Pulmonary involvement occurred at 24 mo (range 2-372) after the onset of MMP. Bronchoscopy revealed acute inflammation during active disease and scarring of the trachea and bronchi in the later stages. Systemic infections occurred in 45%, while pulmonary infection occurred in 36%. Mortality due to respiratory failure, at the median age of 20 years (range 18-76), occurred in 45% of the patients, and was considered disease related. In spite of the young age, while there are some similarities in the clinical profile and response to systemic therapy, there are definitive differences from other patients with MMP. Early diagnosis with appropriate management could produce better clinical outcomes and prevent mortality in this orphan disease. Consequently, there is a critical need for early identification and diagnosis of POPS.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

Predictors of inflammatory lower airway disease in cats presented to the emergency room in respiratory distress: a case-control study.

OBJECTIVES: The objective of the study was to identify whether venous blood gas (VBG) variables may serve as a predictor of inflammatory lower airway disease (ILAD) in cats presenting with respiratory distress. A secondary objective of this study was to compare the diagnostic utility of patient signalment, history and physical examination findings, as compared with VBG variables. METHODS: The medical records of cats presenting with respiratory distress secondary to ILAD (54 cases) and non-ILAD (121 controls) were retrospectively reviewed. RESULTS: No admission VBG variables were predictive of a final diagnosis of ILAD. Comparatively, multivariable analysis identified a history of a cough (P <0.001), increased respiratory rate (P = 0.001), the presence of an abdominal component to respiration (P = 0.007) and the absence of pleural effusion (P <0.01) to be independently associated with a final diagnosis of ILAD. Cats with a history of a cough and an abdominal component to respiration had 7.86 and 5.81 greater odds of being diagnosed with ILAD, respectively. Cats with pleural effusion had 7.43 lower odds of having this final diagnosis. For every 10 breaths/min increase in respiratory rate, cats had 1.48 greater odds of being diagnosed with ILAD. Cats diagnosed with ILAD had a survival rate of 94% (95% CI 84-99%) vs 61% (95% CI 51-70%) for non-ILAD controls (P <0.001). CONCLUSIONS AND RELEVANCE: The results of this study found patient history and physical examination findings to be more useful predictors of a final diagnosis of ILAD in comparison with VBG variables at presentation. A history of a cough, an abdominal component to respiration and a lack of pleural effusion were found to be significant predictors of this diagnosis. Further investigation into the role of respiratory rate in ILAD is warranted.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

Feline Asthma: Diagnostic and Treatment Update.

Asthma is an important allergic lower-airway disease in cats affecting approximately 1% to 5% of the pet cat population. New diagnostics are being developed to help better differentiate asthma from other lower-airway diseases and improve monitoring. In addition, new treatments are being developed to help in refractory cases or in those cases in which traditional therapeutics are contraindicated. This article discusses potential pitfalls in the diagnosis of asthma. In addition, current literature investigating new diagnostic tests and therapies for feline asthma is reviewed.

Comparison of signalment, clinical, laboratory and radiographic parameters in cats with feline asthma and chronic bronchitis.

OBJECTIVES: Feline asthma (FA) and feline chronic bronchitis (CB) are common respiratory conditions in cats, frequently referred to as 'feline lower airway disease'. However, the aetiologies of both inflammatory airway diseases are probably different. Little is known about the differences in signalment, clinical signs, laboratory abnormalities and radiographic features between cats with these two airway diseases. The aim of the study was to investigate whether certain parameters can help in differentiating between both diseases, as distinguished by airway cytology. METHODS: Seventy-three cats with FA and 24 cats with CB were included in the retrospective study. Inclusion criteria were compatible clinical signs and a cytological evaluation of bronchoalveolar lavage fluid indicating either FA (eosinophilic inflammation) or CB (neutrophilic inflammation) without cytological or microbiological evidence of bacterial infection. Parameters of signalment, physical examination, haematology and thoracic radiographs of both disease groups were compared statistically (P <0.05). RESULTS: The median age of cats with FA was 6 years, and was 7.5 years in cats with CB (P = 0.640). The most commonly reported clinical signs in both groups were a cough (95% FA/96% CB; P = 1.000), pathological pulmonary auscultatory sounds (82% FA/79% CB; P = 0.766) and dyspnoea (73% FA/79% CB; P = 0.601). Abnormal radiographic lung patterns were detected in 94% of cats with FA and 91% with CB (P = 0.629), respectively. Blood eosinophilia was significantly more common in cats with FA (40%) compared with CB (27%) (P = 0.026). CONCLUSIONS AND RELEVANCE: The study indicates that a differentiation of FA and CB by means of signalment, a single clinical sign, and haematological and radiographic findings is not possible.

Bacterial Pneumonia in Dogs and Cats: An Update.

Bacterial pneumonia is a common clinical diagnosis in dogs but seems to occur less often in cats. Underlying causes include viral infection, aspiration injury, foreign body inhalation, and defects in clearance of respiratory secretions. Identification of the specific organisms involved in disease, appropriate use of antibiotics and adjunct therapy, and control of risk factors for pneumonia improve management.

Feline asthma and heartworm disease: Clinical features, diagnostics and therapeutics.

PRACTICAL RELEVANCE: For feline practitioners, the cat with a cough or respiratory distress and thoracic radiographs with a bronchial or bronchointerstitial pattern suggests lower airway disease. Two important differentials, allergic asthma and heartworm disease (HWD), have many overlapping clinicopathologic features, but also clear and important differences in terms of cause and disease progression, treatment and prognosis. Notably, asthma is readily treatable and HWD is preventable. CLINICAL SIGNIFICANCE: Feline HWD comprises two clinical syndromes: the comparatively recently described heartworm-associated respiratory disease (HARD) and adult HWD. The former is much more common; very few cats with HARD develop adult HWD. In HARD, following death of immature worms, pulmonary lesions may improve over time ('self-cure'). Lesions of adult HWD also improve over time as long as reinfection does not occur; however, with death of adult heartworms, mortality is high, and the prognosis is guarded. In asthma, morbidity is relatively high, but mortality is low, with an overall good to excellent prognosis. DISEASE RECOGNITION: Feline asthma is encountered worldwide. In the authors' impression, feline HWD is often under-recognized. AIMS: The aim of this review is to assist clinicians in differentiating feline asthma from feline HWD; as such, the emphasis is on distinguishing clinical features, as well as on diagnostics, therapy and prognosis. In differentiating these conditions, clinicians can attempt the goal of properly managing these diseases and can best educate owners on prognosis. EVIDENCE BASE: For both feline asthma and feline HWD, the authors have drawn on the available peer-reviewed literature studies involving experimental models as well as spontaneous disease.

Owner-reported coughing and nasal discharge are associated with clinical findings, arterial oxygen tension, mucus score and bronchoprovocation in horses with recurrent airway obstruction in a field setting.

REASONS FOR PERFORMING STUDY: In clinical practice, veterinarians often depend on owner-reported signs to assess the clinical course of horses with recurrent airway obstruction (RAO). OBJECTIVES: To test whether owner-reported information on frequency of coughing and observation of nasal discharge are associated with clinical, cytological and bronchoprovocation findings in RAO-affected horses in nonstandardised field conditions. STUDY DESIGN: Cross-sectional study comparing healthy and RAO-affected horses. METHODS: Twenty-eight healthy and 34 RAO-affected Swiss Warmblood horses were grouped according to owner-reported 'coughing frequency' and 'nasal discharge'. Differences between these groups were examined using clinical examination, blood gas analyses, endoscopic mucus scores, cytology of tracheobronchial secretion and bronchoalveolar lavage fluid, and airway hyperresponsiveness determined by plethysmography with histamine bronchoprovocation. RESULTS: Frequently coughing horses differed most markedly from healthy control animals. Histamine bronchoprovocation-derived parameters were significantly different between the healthy control group and all RAO groups. Mucus grades and tracheobronchial secretion and bronchoalveolar lavage fluid neutrophil percentages had particularly high variability, with overlap of findings between groups. Owner satisfaction with the clinical status of the horse was high, even in severely affected horses. CONCLUSIONS: Owner-reported coughing and nasal discharge are associated with specific clinical and diagnostic findings in RAO-affected horses in field settings. While airway hyperresponsiveness differentiates best between healthy horses and asymptomatic RAO-affected horses, the absence of coughing and nasal discharge does not rule out significant neutrophilic airway inflammation. Owner satisfaction with the clinical status of the horse was uninformative.

Update on feline asthma.

This article provides an overview of recent advances in the diagnosis and treatment of feline asthma. The authors discuss the potential pitfalls in the diagnosis of feline asthma. In addition, current literature investigating new therapies for the treatment of feline asthma is reviewed.

Bacterial pneumonia in dogs and cats.

Bacterial pneumonia is a common clinical diagnosis in dogs but seems to occur less commonly in cats. Underlying causes include viral infection, aspiration injury, and foreign body inhalation. Identification of the organisms involved in disease, appropriate use of antibiotics and adjunct therapy, and control of risk factors for pneumonia improve management.