Behaviour change interventions for physical activity in adults with chronic obstructive pulmonary disease; A systematic review and meta-analysis.

BACKGROUND: Physical activity in adults with COPD is poor, but behaviour change interventions could help improve activity. This systematic review aims to examine behaviour change interventions to promote physical activity and health outcomes for adults with COPD. METHODS: Eight databases were searched from inception until April 2023: Web of Science, CENTRAL, MEDLINE, EMBASE, APA PsychINFO, CINAHL, PROSPERO, Cochrane Airways Trials Register. Relevant studies were appraised to determine the impact of behaviour change interventions on physical activity outcomes. Interventions were mapped to Michie's Theoretical Domains Framework (TDF) and a meta-analysis and narrative synthesis conducted. The Cochrane risk of bias tool 2 and the GRADE criteria evaluated bias and the quality and certainty of the evidence. RESULTS: Twelve randomized controlled trials (RCTs) were included in the review (n = 1211). The most frequently utilized behaviour change interventions included counselling, stepcount monitoring, social support and goal setting. The most commonly measured outcomes across studies were steps-per-day, physical activity levels, exercise capacity and quality of life. A meta-analysis of comparable studies demonstrated there was no difference in stepcount in favour of behaviour change interventions with respect to steps-per-day (SMD 0.16, 95 % CI -0.03, 0.36; p = 0.10). There was some evidence of short-term improvement in physical activity and quality of life, with behaviour change interventions related to goals, behaviour regulation and social influences. CONCLUSIONS: People with COPD may benefit from behaviour change interventions to increase physical activity and quality of life in the short-term. The overall certainty and quality of the evidence is low.

Behaviour change and physical activity interventions for physical activity engagement in community dwelling adults with chronic obstructive pulmonary disease: protocol for a systematic review.

Background: Chronic obstructive pulmonary disease (COPD) is a complex respiratory disease and the third leading cause of death worldwide. Pulmonary rehabilitation is recognised as the gold standard of care in the management of COPD, however engagement with pulmonary rehabilitation is low and maintenance of a physically active lifestyle in community dwelling adults with COPD is poor. Supporting positive behaviour change in people with COPD could help to increase their engagement with physical activity. This systematic review will examine behaviour change and physical activity interventions delivered to community dwelling adults with COPD with the aim of increasing physical activity engagement. Interventions will be mapped against Michie's theoretical domains framework (TDF) to inform clinical practice and health policy. Methods: The following databases will be searched from inception until December 2021: Web of Science, CENTRAL, MEDLINE (via EBSCO), EMBASE, APA PsychINFO, CINAHL (via EBSCO), AMED, PROSPERO, Cochrane Airways Trials Register. Reference lists of the relevant studies and grey literature will be searched using Grey Literature Report, Open Grey and Google Scholar search engines. Relevant studies will be systematically reviewed and subject to quality appraisal to determine the impact of behaviour change and physical activity interventions on outcomes of community-dwelling adults with COPD. Interventions will be mapped to Michie's TDF and a narrative synthesis with respect to nature, effectiveness on target population and setting/environment will be provided. Findings will be reported in relation to the generalisability of the primary results and research question, and will include secondary findings on quality of life, self-reported participation in physical activity, exercise capacity, adverse events and intervention adherence. The review will be presented according to the PRISMA guidelines 2020. Conclusions: This systematic review is necessary to explain the impact of behaviour change and physical activity interventions on outcomes of community dwelling people with COPD. PROSPERO registration: CRD42021264965 (29.06.2021).

Fluctuating hypercalcaemia caused by cavitary Mycobacterium bovis pulmonary infection.

Hypercalcaemia occurs in many granulomatous diseases. Among them, sarcoidosis and tuberculosis are the most common causes. Other causes include berylliosis, coccidioidomycosis, histoplasmosis, Crohn's disease, silicone-induced granulomas, cat-scratch disease, Wegener's granulomatosis and Pneumocystis carinii pneumonia. Hypercalcaemia in granulomatous disease occurs as a consequence of dysregulated production of 1,25-(OH)2 D3 (calcitriol) by activated macrophages in granulomas. Hypercalcaemia in patients with Mycobacterium tuberculosis infection has been reported in 0%-28% of cases. Uncultured bronchoalveolar lavage cells from patients with M. tuberculosis produce greater amounts of calcitriol compared with controls. Although Nayar et al described hypercalcaemia in a case of sepsis associated with intravesical Bacille Calmette Guerin therapy, there are no published reports describing hypercalcaemia in patients with pulmonary M. bovis infection. We describe a patient with M. bovis cavitary pulmonary infection with sustained hypercalcaemia that fluctuated and recurred repeatedly over the course of therapy, ultimately culminating in normalisation of serum calcium when therapy had led to cure. Treatment consisted of antituberculous therapy, oral corticosteroids and intravenous bisphosphonates with a favourable outcome.

Biomarkers to identify ILD and predict lung function decline in scleroderma lung disease or idiopathic pulmonary fibrosis.

BACKGROUND: SSc-ILD and IPF demonstrate significant morbidity and mortality. Predicting disease progression is challenging in both diseases. OBJECTIVES: We sought a serum biomarker that could identify patients with SSc-ILD or IPF and prospectively predict short-term decline in lung function in these patients. METHODS: 10 healthy controls, 5 SSc w/o ILD, 6 SSc-ILD and 13 IPF patients underwent venesection. An array of cytokines including KL-6, SP-D and MMP7 were measured. PFTs were obtained at baseline and six months. Cytokine measurements were correlated with PFTs. RESULTS: KL-6 in IPF patients (633 ng/ml, IQR 492-1675) was significantly elevated compared to controls (198 ng/ml, IQR 52-360, p<0.01) and SSc w/o ILD patients (192 ng/ml, IQR 0-524, p<0.05); KL-6 in SSc-ILD patients (836 ng/ml, IQR 431-1303) was significantly higher than in controls (p<0.05). SP-D was significantly higher in IPF patients (542 ng/ml, IQR 305-577) compared to controls (137 ng/ml, IQR 97-284, p<0.01) or to SSc w/o ILD patients (169 ng/ml, IQR 137-219, p<0.05). In comparison with controls (0.0 ng/ml, IQR 0.0-0.6), MMP7 was significantly higher in both IPF patients (2.85 ng/ml, IQR 1.5-3.6, p<0.05) and SSc-ILD patients (5.41 ng/ml, IQR 2.6-7.2, p<0.001). Using a cut-off level of 459ng/ml for KL-6 and of 1.28 ng/ml for MMP7, 18 out of 19 patients with ILD had a serum value of either KL-6 or MMP7 above these thresholds. For all ILD patients, baseline serum SP-D correlated with ΔFVC %pred over six months (r=-0.63, p=0.005, 95% CI -0.85 to -0.24). CONCLUSIONS: Combining KL-6 with MMP7 may be a useful screening tool for patients at risk of ILD. SP-D may predict short-term decline in lung function.

Empyema thoracis from an inhaled peanut.

A 77-year-old man with a history of pulmonary sarcoidosis was referred with persistent cough and reduced air entry on auscultation of the right lung base. He was an ex-smoker with a 40-pack-year history and his general practitioner was concerned about the possibility of bronchogenic carcinoma. A chest radiograph showed a right-sided pleural effusion with right mid-zone airspace opacification. Bronchoscopy revealed a peanut covered in mucus lodged in the right lower lobe bronchus. CT of the thorax demonstrated a multiloculated right pleural effusion with associated compressive atelectasis, consistent with chronic empyema. A chest drain was inserted but failed to fully clear the collection and the patient proceeded to a thoracoscopic decortication of a pleural empyema secondary to the right lower lobe obstruction from an inhaled peanut. His postoperative recovery was uncomplicated.

Holy Saturday asthma.

A 61-year-old man complained of cough and dyspnoea after exposure to colophony-containing solder fumes at work. A histamine challenge test confirmed airway hyper-responsiveness, and colophony-challenge demonstrated a 16.7% drop in peak expiratory flow rate (PEFR), supporting a diagnosis of colophony-induced occupational asthma. At review, the patient presented with cough, dyspnoea and wheeze that occurred acutely when exposed to the fumes from burning incense during Easter Saturday services, necessitating his departure from the church. Inhalation challenge tests using two blends of incense used at his church (Greek and Vatican) led to identical symptoms and a significant reduction in forced expiratory volume in 1 s 15 min after exposure and PEFRs up to 48 h after exposure, indicating an early and late phase asthmatic reaction. This is the first report of coexistent colophony and incense-induced asthma. The similarities in chemical structures between abietic acid in colophony and boswellic acid in incense suggest a common mechanism.

Rare causes of persistent wheeze that mimic poorly controlled asthma.

Upper airway obstruction can present with stridor or expiratory or inspiratory wheeze and is commonly misdiagnosed as asthma. As asthma is common, such cases can remain hidden among patients with lower airway obstruction who attend primary care or respiratory clinics. We describe four causes of upper airway obstruction (paradoxical vocal cord movement, subglottic stenosis, retrosternal goitre and double aortic arch) which were misdiagnosed as 'poorly controlled asthma'.

A case series of patients on chemotherapy with dyspnoea and pulmonary infiltrates.

Clinicians often assume that patients who develop pulmonary symptoms and radiographic infiltrates while receiving cytotoxic chemotherapy have opportunistic pulmonary infection or chemotherapy-related interstitial lung disease. We describe two cases of rare complications of commonly used chemotherapeutic agents (gemcitabine-induced eosinophilic pneumonia and rituximab-induced hypersensitivity pneumonitis) that vindicate this assumption but a third case of scleroderma-associated interstitial lung disease that became clinically manifest in a patient who was receiving chemotherapy. The latter case highlights the need for vigilance for other causes of interstitial lung disease in patients receiving chemotherapy.

Multiple cutaneous nodules as the presenting sign of small cell lung cancer.

We describe a 67-year-old male smoker who presented with an 8 week history of productive cough, dyspnoea on minimal exertion, weight loss of 8 kg and multiple painful cutaneous nodules of varying size and morphology. A chest radiograph showed a mass at the right hilum. A CT examination showed extensive mediastinal lymphadenopathy with encasement of the lower trachea, carina and left main bronchus. The left main bronchus was 95% stenosed and there were multiple liver metastases. Innumerable cutaneous nodules were also seen. A biopsy of one of the cutaneous nodules confirmed metastases from a neuroendocrine lung primary tumour, consistent with extensive stage small cell lung cancer. The patient died soon after diagnosis.

Sorafenib-induced tuberculosis reactivation.

BACKGROUND: Sorafenib is a multikinase inhibitor with an established role in treating renal cell carcinoma and hepatocellular carcinoma. In vivo studies have demonstrated sorafenib's inhibitory effects on various immune cells and cytokines which are essential to the maintenance of latency of granulomas in patients with latent tuberculosis infection. CASE REPORT: A 74-year-old male with clear cell renal cell carcinoma with pulmonary metastases was treated with sorafenib to good effect. However, he developed productive cough, sweats and weight loss. A computed tomography scan of the thorax demonstrated right lower lobe consolidation and cavitation. Sputum analysis was positive for tuberculous smear and culture. A diagnosis of sorafenib-induced tuberculosis reactivation was made. Sorafenib was held and anti-tuberculous antibiotics were commenced, which led to symptomatic and radiographic improvement. CONCLUSION: The authors postulate that sorafenib could increase the risk of progression from latent to active tuberculosis, and urge vigilance and possible screening for latent tuberculosis in patients who are treated with sorafenib.

Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma.

BACKGROUND: Combining inhaled corticosteroids with long-acting beta(2)-agonists results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma. OBJECTIVE: We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling. METHODS: Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment. RESULTS: Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle area. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area. CONCLUSIONS: The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol.

Immunosuppressant-responsive idiopathic lymphocytic pleuritis.

Lymphocyte-dominant pleural inflammation is seen in tuberculous, malignant and immune-mediated pleural disease. We describe two male patients who presented with chest pain and dyspnoea, in whom radiological and histological investigations showed idiopathic lymphocytic pleuritis that responded to immunosuppressive therapy with corticosteroids and/or azathioprine. Corticosteroid-responsive pleuritis has been described in association with many conditions, but little is known of idiopathic lymphocytic pleuritis. The authors suggest that patients with idiopathic pleural thickening undergo early thoracoscopic pleural biopsy, and that immunosuppressant therapy be considered for patients with idiopathic lymphocytic pleuritis.

The role of substance P in inflammatory disease.

The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease.

Airways obstruction in survivors of thoracoplasty: reversibility is greater in non-smokers.

OBJECTIVE: Before the advent of antituberculous chemotherapy, thoracoplasty (TPL) was the definitive form of therapy for cavitary pulmonary tuberculosis. This study aimed to characterize the late functional sequelae of TPL, and to establish the degree of reversibility of any consequent airway obstruction. METHODOLOGY: Pulmonary function was studied in 21 long-term (mean 35 years) survivors of TPL between the years 1990-2001. RESULTS: A mixed obstructive/restrictive defect was found in this patient cohort. After inhalation of bronchodilator, marginal increases in FEV(1) and FVC and marginal decreases in FRC, RV and TLC were observed. Maximum mid-expiratory flow rate was severely reduced (28.8% of predicted), but reversibility after inhaled beta(2)-agonist was highest for this parameter of pulmonary function (mean 11%). Smokers had a higher RV (P = 0.04), suggesting hyperinflation, while non-smokers had a larger increase in FEV(1)/FVC ratio postbronchodilator (P = 0.004), suggesting more marked reversibility of airways obstruction in this group. CONCLUSIONS: Long-term survivors of TPL have an obstructive as well as a restrictive ventilatory defect. These patients have partial reversibility of the obstructive defect. The degree of reversibility found suggests that bronchodilator therapy may help these patients.

Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-alpha in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared with 8/10 patients with sarcoidosis (p = 0.012) and 2/9 biopsies of controls compared with 9/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.