Ryan Hoy

Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life

Little is known about how comorbidities affect difficult asthma patients across different domains of asthma outcomes. We hypothesized that comorbidities in difficult asthma significantly influence asthma outcomes.

Work-associated irritable larynx syndrome

BACKGROUND Work-associated respiratory symptoms may be caused by disorders of both the lower and upper respiratory tract. We propose that occupational exposures may initiate and/or trigger recurrent hyperkinetic laryngeal symptoms, predominantly episodic dyspnoea, dysphonia, cough and sensation of tension in the throat-work-associated irritable larynx syndrome (WILS). AIMS To examine characteristics of individual and work-related factors that are associated with WILS, occupational asthma (OA) and work-exacerbated asthma (WEA). METHODS Subjects with WILS, OA and WEA were identified from an occupational lung disease clinic. A review of 448 charts of patients attending the clinic between 2002 and 2006 was undertaken, with information entered onto a standardized abstraction form. RESULTS Fifty subjects were identified with OA, 40 with WEA and 30 with WILS. Subjects with the diagnosis of WILS were more likely to be female and more frequently reported symptoms of gastro-oesophageal reflux. The most common triggers of workplace symptoms in the WILS group were odours, fumes, perfumes and cleaning agents. Fourteen patients with WILS identified a specific precipitating event at the workplace at the time of the onset of their symptoms and five of these subjects presented to an emergency department within 24 h of the event. CONCLUSIONS Dysfunction of the upper airway is an important cause of work-associated respiratory symptoms. The identification and management of WILS requires a multidisciplinary approach with a focus on modifying work-related and intrinsic factors that may perpetuate symptoms.

A case of certolizumab-induced interstitial lung disease in a patient with rheumatoid arthritis

SIR, A 66-year-old non-smoking woman with a 35-year history of widespread erosive RA presented with rapidly progressive breathlessness. Her previous therapy had included CYC in the early 1990s, complicated by the development of haemorrhagic cystitis requiring bladder reconstruction in 1995. She had no other major medical history. Until 6 months prior to presentation, she had been taking MTX 20 mg weekly for 12 years and prednisolone 2.5 10 mg/day. In the setting of recurrent joint inflammation, LEF 20 mg/day was added to her therapy and her MTX was increased to 30 mg weekly. Two months later the patient had ongoing severe joint inflammation. Investigations revealed an anti-CCP antibody titre of >250 U/ml (normal< 20), a CRP titre of 13 mg/l (normal< 5), a normal chest X-ray (Fig. 1a) and negative Quantiferon-Gold assay. The following month, 400 mg of certolizumab subcutaneously administered every 4 weeks was begun. At presentation she described a 1-month coryzal illness. Breathlessness and dry cough had developed over the preceding 2 weeks, causing difficulty with minor exertion, such as dressing. On examination she demonstrated an oxygen saturation of 89% on room air, was afebrile and had an increased respiratory rate of 24. Basal crackles were audible within the chest. Peripheral examination demonstrated extensive erosive joint disease, maximal at the hands and feet. A CT chest taken at presentation demonstrated bilateral ground glass and reticular change involving both lungs, maximally in the lower zones (Fig. 1b and c and supplementary figures, available at Rheumatology Online). Blood tests revealed a total white cell count within normal limits, a CRP of 28 (normal< 5) and an ESR of 77 mm/h (normal 5 20 mm/h). She had a CCP antibody titre of 107 U/ml. Sputum culture could not be obtained and blood cultures were negative. Treatment was initiated in a provincial hospital for presumed Pneumocystis pneumonia, using high-dose cotrimoxazole and prednisolone 50 mg orally daily, without clinical or objective improvement. On transfer to our hospital, surgical lung biopsy was performed and features consistent with organizing pneumonia were demonstrated. Histological features included thickening of the alveolar walls with areas of fibrosis with a mild myxomatous component. Only a light infiltrate of inflammatory cells was seen and there was no evidence of vasculitis or granuloma formation. PCR testing for Pneumocystis DNA was negative and fungal and bacterial cultures were negative. The patient was treated with i.v. methylprednisolone 1 g/day for 3 days and thereafter prednisolone 30 mg twice daily. She remained hypoxic and oxygen dependent throughout her admission, but 1 month after presentation, had not significantly deteriorated. A repeat CT chest performed 1 month following her initial CT scan demonstrated changes restricted to those areas that had been involved at presentation (Fig. 1d and supplementary figures, available at Rheumatology Online). Significant architectural distortion and traction bronchiectasis had developed in those areas in keeping with rapidly evolving fibrosis. She was discharged back to her provincial hospital for restorative care prior to discharge home. She remained oxygen dependent at the time of discharge. At review 1 month post-discharge, having received prednisolone 1 mg/kg through that period, the patient had not made any clinical improvement, with ongoing exertional hypoxia and a total walk distance on the 6-min walk test of 88 m, consistent with severe functional impairment. Two months after review the patient entered palliative care and died shortly thereafter. TNF-a inhibitors provide an important means for disease control in patients with RA not responding to DMARDs, reducing the risk of joint damage and improving physical function and quality of life [1]. Certolizumab is composed of the Fab antigen-binding domain of a humanized monoclonal anti-TNF antibody combined with polyethylene glycol to increase its half-life. It demonstrates equivalent efficacy to the other TNF-a inhibitors [2]. Pulmonary adverse effects of TNF-a inhibitor therapy include well-documented infectious complications, specifically mycobacterial infection [3]. Non-infectious complications include a range of interstitial lung diseases, including usual interstitial pneumonia, non-specific interstitial pneumonia, organizing pneumonia, lymphocytic interstitial pneumonia and diffuse alveolar damage [4]. This case represents the first description of certolizumab-induced pulmonary toxicity [5]. In conjunction with descriptions attached to each of the other TNF-a inhibitors, the risk of pneumonitis displays a class effect. Our patient demonstrated a number of features that have been recognized as risk factors for TNF-a inhibitorassociated pneumonitis, including age >60, female sex and concomitant disease-modifying agent use. Of note is the absence of pre-existing interstitial lung disease, a risk factor highlighted in one large case series [4]. In addition, this patient’s disease displayed a faster time of onset than occurred in that series, within which disease occurred generally only after 6 months. Despite aggressive immunosuppression, our patient displayed ongoing severe debility and persistent interstitial change in keeping with data from larger series, within which approximately one-third of cases have displayed no resolution.

Validated questionnaires heighten detection of difficult asthma comorbidities

ABSTRACT Objective: Multiple extra-pulmonary comorbidities contribute to difficult asthma, but their diagnosis can be challenging and time consuming. Previous data on comorbidity detection have focused on clinical assessment, which may miss certain conditions. We aimed to locate relevant validated screening questionnaires to identify extra-pulmonary comorbidities that contribute to difficult asthma, and evaluate their performance during a difficult asthma evaluation. Methods: MEDLINE was searched to identify key extra-pulmonary comorbidities that contribute to difficult asthma. Screening questionnaires were chosen based on ease of use, presence of a cut-off score, and adequate validation to help systematically identify comorbidities. In a consecutive series of 86 patients referred for systematic evaluation of difficult asthma, questionnaires were administered prior to clinical consultation. Results: Six difficult asthma comorbidities and corresponding screening questionnaires were found: sinonasal disease (allergic rhinitis and chronic rhinosinusitis), vocal cord dysfunction, dysfunctional breathing, obstructive sleep apnea, anxiety and depression, and gastro-oesophageal reflux disease. When the questionnaires were added to the referring clinicians impression, the detection of all six comorbidities was significantly enhanced. The average time for questionnaire administration was approximately 40 minutes. Conclusions: The use of validated screening questionnaires heightens detection of comorbidities in difficult asthma. The availability of data from a battery of questionnaires prior to consultation can save time and allow clinicians to systematically assess difficult asthma patients and to focus on areas of particular concern. Such an approach would ensure that all contributing comorbidities have been addressed before significant treatment escalation is considered.

Outcome of work-related asthma exacerbations in Quebec and Ontario

There are differences in the management of workers with work-related asthma within Canadian provinces. In Quebec, the compensation of a case of occupational asthma is usually based on the positivity of a specific inhalation challenge, whereas in Ontario, the diagnosis is usually based on serial peak expiratory flow (PEF), provocative methacholine concentration causing a 20% decrease in forced expiratory volume in 1 s (PC20) monitoring at and away from work, and specific skin-prick tests (that is, less often on specific inhalation challenges) [1]. We aimed: 1) to compare the delay between the onset of work-related asthma symptoms and the diagnosis of occupational asthma and work-exacerbated asthma between Quebec and Ontario; and 2) to assess and compare the healthcare utilisation in subjects with occupational asthma and work-exacerbated asthma between the provinces before and after the first assessment in two tertiary clinics in Quebec and Ontario that specialise in work-related asthma. Diagnosing work-related asthma decreased asthma-related healthcare utilisation in Quebec and Ontario http://ow.ly/CFrPk

Work-related laryngeal syndromes

Purpose of reviewThis review summarizes recent literature regarding the association of nonorganic laryngeal dysfunction with occupational exposures. Laryngeal dysfunction may masquerade as asthma and is an important consideration in patients with work-associated respiratory symptoms. Recent findingsAlthough there is lack of consensus regarding clinical features, vocal cord dysfunction (VCD) is the most well appreciated form of nonorganic laryngeal dysfunction. There are significant gaps in the literature regarding the occupational epidemiology of laryngeal dysfunction, however, occupational exposures such as upper airway irritants may be associated with the onset of symptoms. Recurrent work-associated laryngeal dysfunction has been described in occupational groups including the military and professional athletes. Recent theories have considered that VCD may be a state of laryngeal hyperresponsiveness associated with both intrinsic and extrinsic factors. SummaryLaryngeal dysfunction is an important consideration in patients with work-associated respiratory symptoms. Clinicians should have a high index of suspicion, in particular, if symptoms are associated with exposure to a respiratory irritant. Situations of high psychological stress may also be associated with recurrent symptoms. There is a requirement for evidence-based guidelines for the diagnosis and management of laryngeal dysfunction, which should also address work-related factors.

Occupational exposures and the development of new-onset asthma: a population-based cohort study from the ages of 13 to 44 years.

Objective: To evaluate the risk of asthma associated with occupational exposures in a population-based cohort. Methods: The risk of asthma was analyzed in 792 subjects who were asthma free at the age of 13 years. Occupational histories were obtained from subjects at the age of 44 years and occupational exposures determined with an asthma-specific job exposure matrix. Cumulative exposure to latex and risk of asthma was examined using Cox proportional hazards regression. Results: Development of asthma was modestly related to exposure at any time to high molecular weight latex (odds ratio, 1.4; 95% confidence interval, 0.9–2.3). Cumulative latex exposure of 6 to 15 years was associated with a hazard ratio of 1.6 for the development of asthma and after 16 years increased to 2.65 (95% confidence interval, 1.28–5.47). Conclusion: There is a significant association between cumulative occupational exposure to latex and new-onset asthma.

Artificial stone-associated silicosis: a rapidly emerging occupational lung disease

Introduction Artificial stone is an increasingly popular material used to fabricate kitchen and bathroom benchtops. Cutting and grinding artificial stone is associated with generation of very high levels of respirable crystalline silica, and the frequency of cases of severe silicosis associated with this exposure is rapidly increasing. Aim To report the characteristics of a clinical series of Australian workers with artificial stone-associated silicosis. Methods Respiratory physicians voluntarily reported cases of artificial stone-associated silicosis identified in their clinical practices. Physicians provided information including occupational histories, respiratory function tests, chest radiology and histopathology reports, when available. Results Seven male patients were identified with a median age of 44 years (range 26–61). All were employed in small kitchen and bathroom benchtop fabrication businesses with an average of eight employees (range 2–20). All workplaces primarily used artificial stone, and dust control measures were poor. All patients were involved in dry cutting artificial stone. The median duration of exposure prior to symptoms was 7 years (range 4–10). Six patients demonstrated radiological features of progressive massive fibrosis. These individuals followed up over a median follow-up period of 16 months (IQR 21 months) demonstrated rapid decline in prebronchodilator forced expiratory volume in 1 s of 386 mL/year (SD 204 mL) and forced vital capacity of 448 mL/year (SD 312 mL). Conclusions This series of silicosis in Australian workers further demonstrates the risk-associated high-silica content artificial stone. Effective dust control and health surveillance measures need to be stringently implemented and enforced in this industry.

Population-wide preventive interventions for reducing the burden of chronic respiratory disease.

Chronic obstructive pulmonary disease and asthma impose a substantial burden of disease. This narrative review focuses on potential population-wide interventions that are likely to have an impact on these diseases. The developmental origins of adult disease commence in utero, with maternal nutrition being of particular interest. However, to date, trials of maternal allergen avoidance, dietary supplementation or probiotics have not shown consistent protective effects against asthma. Poor indoor air quality, especially from biomass fuels as well as second-hand tobacco smoke, is a well-recognised risk factor for chronic respiratory diseases. This can be modified by cleaner fuels, cooking stoves or heaters, and improved ventilation. Although allergens are a risk factor for childhood asthma, the results of interventions to reduce exposures have been disappointing. Traffic-related air pollution is associated with an increased incidence of asthma in children. Primary prevention of the adverse effects of air pollution has focused on the development of ambient air quality guidelines, but enforcement remains a challenge in many countries. Occupational asthma may be induced by sensitisers or irritants in the workplace. Prevention involves eliminating the agent or reducing exposure as far as possible, which is more effective than respiratory protective equipment. Smoking cessation remains a key proven preventive strategy for chronic respiratory diseases. There is now an international framework for tobacco control, and recent innovations include plain packaging of tobacco. Chronic respiratory diseases can be substantially prevented by the above population-wide interventions.

Nonadherence in the era of severe asthma biologics and thermoplasty

Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty. Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking >75% of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period. Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data; including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%). At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies. Preventer adherence is underrecognised and must be confirmed objectively prior to initiating novel asthma treatment http://ow.ly/Kc1X30iysYD