Journal Articles
Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915
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Item Causes and MEchanisms foR non-atopic Asthma in Children (CAMERA) study: rationale and protocol(BioMed Central Ltd, 2025-12-01) Njoroge M; Pinheiro GP; Santana CVN; Ali H; Hobbs S; Mena-Bucheli S; Romero-Sandoval N; Robertson S; Rutter CE; Davoren D; Brooks C; Douwes J; Cooper PJ; Mpairwe H; Figueiredo CA; Cruz AA; Barreto ML; Pearce N; Pembrey L; CAMERA study groupBACKGROUND: The Causes And MEchanisms foR non-atopic Asthma in children (CAMERA) study was designed to investigate risk factors and mechanisms of non-atopic asthma in children and young adults in Brazil, Ecuador, Uganda, and New Zealand. Initial epidemiological analyses using existing datasets identified and compared risk factors for both atopic and non-atopic asthma. The focus of this paper is the protocol for sample collection and analysis of clinical data on possible non-atopic mechanisms. METHODS: In each of the four centres, the CAMERA study will enroll 160 participants aged 10-28 years, equally distributed among atopic asthmatics (AA), non-atopic asthmatics (NAA), atopic non-asthmatics and non-atopic non-asthmatics. Participants will be new recruits or returning World ASthma Phenotypes (WASP) study participants. Phase I consists of skin prick tests to define atopy, a general CAMERA questionnaire that covers respiratory and general health to identify asthma cases, followed by an asthma control questionnaire for asthmatics only. Phase II consists of a stress questionnaire and the following clinical assessments: lung function, nasal cytology, blood sampling, in vitro whole blood stimulation to assess IFN-γ production, hair cortisol concentration, dry air and capsaicin challenges, plus in a subset, cold air challenges. Analyses will compare inflammatory, physiological and clinical parameters across the four groups overall and by country. DISCUSSION: Here, we present the protocol for the CAMERA study, to provide relevant methodological details for CAMERA publications and to allow other centres globally to conduct similar analyses. The findings of this mechanistic multi-centre study will inform new and phenotype-specific prevention and treatment approaches. CLINICAL TRIAL NUMBER: Not applicable.Item A perspective on green, blue, and grey spaces, biodiversity, microbiota, and human health.(Elsevier B.V., 2023-09-20) Potter JD; Brooks C; Donovan G; Cunningham C; Douwes JHumans have lived from equator to poles for millennia but are now increasingly intruding into the wild spaces of other species and steadily extruding ourselves from our own wild spaces, with a profound impact on: our relationship with the natural world; survival of other species; pollution; climate change; etc. We have yet to grasp how these changes directly impact our own health. The primary focus of this paper is on the beneficial influence of proximity to the natural environment. We summarize the evidence for associations between exposure to green space and blue space and improvements in health. In contrast, grey space - the urban landscape - largely presents hazards as well as reducing exposure to green and blue space and isolating us from the natural environment. We discuss various hypotheses that might explain why green, blue, and grey space affect health and focus particularly on the importance of the biodiversity hypothesis and the role of microbiota. We discuss possible mechanisms and exposure routes - air, soil, and water. We highlight the problem of exposure assessment, noting that many of our current tools are not fit for the purpose of understanding exposure to green and blue space, aerosols, soils, and water. We briefly discuss possible differences between indigenous perspectives on the nature of our relationship with the environment and the more dominant international-science view. Finally, we present research gaps and discuss future directions, particularly focusing on the ways in which we might - even in the absence of a full understanding of the mechanisms by which blue, green, and grey space affect our health - begin to implement policies to restore some balance to our environment of with the aim of reducing the large global burden of ill health.Item Gut microbiome signature and nasal lavage inflammatory markers in young people with asthma(Elsevier Inc on behalf of the American Academy of Allergy, Asthma & Immunology (AAAAI), 2024-05) Sampaio Dotto Fiuza B; Machado de Andrade C; Meirelles PM; Santos da Silva J; de Jesus Silva M; Vila Nova Santana C; Pimentel Pinheiro G; Mpairwe H; Cooper P; Brooks C; Pembrey L; Taylor S; Douwes J; Cruz ÁA; Barreto ML; Pearce N; Figueiredo CAVBACKGROUND: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation. OBJECTIVE: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals. METHODS: Stool and nasal lavage samples were collected from 29 children and adolescents with type 2 asthma and 28 children without asthma in Brazil. Amplicon sequencing of the stool bacterial V4 region of the 16S rRNA gene was performed using Illumina MiSeq. Microbiota analysis was performed by QIIME 2 and PICRUSt2. Type 2 asthma phenotype was characterized by high sputum eosinophil counts and positive skin prick tests for house dust mite, cockroach, and/or cat or dog dander. The nasal immune marker profile was assessed using a customized multiplex panel. RESULTS: Stool microbiota differed significantly between asthmatic and nonasthmatic participants (P = .001). Bacteroides was more abundant in participants with asthma (P < .05), while Prevotella was more abundant in nonasthmatic individuals (P < .05). In people with asthma, the relative abundance of Bacteroides correlated with IL-4 concentration in nasal lavage samples. Inference of microbiota functional capacity identified differential fatty acid biosynthesis in asthmatic compared to nonasthmatic subjects. CONCLUSION: The stool microbiota differed between asthmatic and nonasthmatic young people in Brazil. Asthma was associated with higher Bacteroides levels, which correlated with nasal IL-4 concentration.Item Respiratory symptoms and use of dust-control measures in New Zealand construction workers - A cross-sectional study(PLOS, 7/04/2022) Keer S; Brooks C; Glass B; McLean D; Harding E; Douwes JDust-exposed construction workers have an increased risk of respiratory symptoms, but the efficacy of dust-control measures remains unclear. This study compared respiratory symptoms, using a modified European Community Respiratory Health Survey questionnaire, between construction workers (n = 208) and a reference group of bus drivers and retail workers (n = 142). Within the construction workers, we assessed the effect of collective (on-tool vacuum/'wet-cut' systems) and personal (respirators) exposure controls on symptom prevalence. Logistic regression assessed differences between groups, adjusted for age, ethnicity, and smoking status. Construction workers were more likely to cough with phlegm at least once a week (OR 2.4, 95% CI 1.2-4.7) and cough with phlegm ≥3 months/year for ≥2 years (OR 2.8, CI 1.2-7.0), but they had similar or fewer asthma symptoms. Construction workers who had worked for 11-20 years reported more cough/phlegm symptoms (OR 5.1, 1.7-15.0 for cough with phlegm ≥3 months/year for ≥2 years) than those who had worked <10 years (OR 1.9, 0.6-5.8), when compared to the reference group. Those who used 'wet-cut' methods reported less cough with phlegm, although the evidence for this association was weak (OR 0.4, CI 0.2-1.1 for cough with phlegm at least once a week); use of on-tool extraction showed a similar trend. No associations between respiratory protective equipment-use and symptoms were found. In conclusion, construction workers reported more symptoms suggestive of bronchitis, particularly those employed in the industry for >10 years. Use of collective dust exposure controls might protect against these symptoms, but this requires confirmation in a larger study.Item Enhanced airway sensory nerve reactivity in non-eosinophilic asthma(BMJ Publishing Group Ltd and the British Thoracic Society, 2/11/2021) Ali H; Brooks C; Crane J; Beasley R; Holgate S; Gibson P; Pattemore P; Tzeng Y-C; Stanley T; Pearce N; Douwes JBACKGROUND: Neural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics. METHODS: Thirty-eight asthmatics and 19 non-asthmatics (aged 14-21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs. RESULTS: Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0; p<0.05). NEA tended to also have greater capsaicin sensitivity than EA, with the difference in capsaicin sensitivity between NEA and EA being of similar magnitude (58.3 µM, 24.1 to 141.5 vs 191.0 µM, 70.9 to 514.0) to that observed between NEA and non-asthmatics; however, this did not reach statistical significance (p=0.07). FEV1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control or treatment were observed. CONCLUSION: NEA, but not EA, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of NEA.Item Asthma inflammatory phenotypes on four continents: most asthma is non-eosinophilic(Oxford University Press on behalf of the International Epidemiological Association, 2023-04) Pembrey L; Brooks C; Mpairwe H; Figueiredo CA; Oviedo AY; Chico M; Ali H; Nambuya I; Tumwesige P; Robertson S; Rutter CE; van Veldhoven K; Ring S; Barreto ML; Cooper PJ; Henderson J; Cruz AA; Douwes J; Pearce N; WASP Study GroupBACKGROUND: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). METHODS: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. RESULTS: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. CONCLUSIONS: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.Item Serum biomarkers of neuroinflammation and blood-brain barrier leakage in amyotrophic lateral sclerosis(BioMed Central Ltd, 2022-12) Cao MC; Cawston EE; Chen G; Brooks C; Douwes J; McLean D; Graham ES; Dragunow M; Scotter ELAmyotrophic lateral sclerosis (ALS) is an incurable and rapidly progressive neurological disorder. Biomarkers are critical to understanding disease causation, monitoring disease progression and assessing the efficacy of treatments. However, robust peripheral biomarkers are yet to be identified. Neuroinflammation and breakdown of the blood-brain barrier (BBB) are common to familial and sporadic ALS and may produce a unique biomarker signature in peripheral blood. Using cytometric bead array (n = 15 participants per group (ALS or control)) and proteome profiling (n = 6 participants per group (ALS or control)), we assessed a total of 106 serum cytokines, growth factors, and BBB breakdown markers in the serum of control and ALS participants. Further, primary human brain pericytes, which maintain the BBB, were used as a biosensor of inflammation following pre-treatment with ALS serum. Principal components analysis of all proteome profile data showed no clustering of control or ALS sera, and no individual serum proteins met the threshold for statistical difference between ALS and controls (adjusted P values). However, the 20 most changed proteins between control and ALS sera showed a medium effect size (Cohen's d = 0.67) and cluster analysis of their levels together identified three sample subsets; control-only, mixed control-ALS, and ALS-only. These 20 proteins were predominantly pro-angiogenic and growth factors, including fractalkine, BDNF, EGF, PDGF, Dkk-1, MIF and angiopoietin-2. S100β, a protein highly concentrated in glial cells and therefore a marker of BBB leakage when found in blood, was unchanged in ALS serum, suggesting that serum protein profiles were reflective of peripheral rather than CNS biofluids. Finally, primary human brain pericytes remained proliferative and their secretome was unchanged by chronic exposure to ALS serum. Our exploratory study suggests that individual serum cytokine levels may not be robust biomarkers in small studies of ALS, but that larger studies using multiplexed analysis of pro-angiogenic and growth factors may identify a peripheral signature of ALS pathogenesis.