Publications by authors named "Imran Sulaiman"

39 Publications

Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome.

medRxiv 2021 Feb 26. Epub 2021 Feb 26.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.
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http://dx.doi.org/10.1101/2021.02.23.21252221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924286PMC
February 2021

Functional lower airways genomic profiling of the microbiome to capture active microbial metabolism.

Eur Respir J 2021 Jan 14. Epub 2021 Jan 14.

Division of Pulmonary, Critical Care, & Sleep Medicine, Department of Medicine, New York University School of Medicine, NY, USA

Rationale: Microbiome studies of the lower airway based on bacterial 16S rRNA gene sequencing assess microbial community structure but can only infer functional characteristics. Microbial products, such as short chain fatty acids (SCFAs), in the lower airways have significant impact on the host's immune tone. Thus, functional approaches to the analyses of the microbiome are necessary.

Methods: Here we used upper and lower airway samples from a research bronchoscopy smoker cohort. In addition, we validated our results in an experimental mouse model.

Measurements: We extended our microbiota characterisation beyond 16S rRNA gene sequencing with the use of whole genome (WGS) and RNA metatranscriptome sequencing. Short chain fatty acids (SCFA) were also measured in lower airway samples and correlated with each of the sequencing datasets. In the mouse model, 16S rRNA gene and RNA metatranscriptome sequencing were performed.

Main Results: Functional evaluations of the lower airway microbiota using inferred metagenome, WGS and metatranscriptome were dissimilar. Comparison with measured levels of SCFAs shows that the inferred metagenome from the 16S rRNA gene sequencing data was poorly correlated, while better correlations were noted when SCFAs levels were compared with WGS and metatranscriptome. Modelling lower airway aspiration with oral commensals in a mouse model showed that the metatranscriptome most efficiently captures transient active microbial metabolism, which was overestimated by 16S rRNA gene sequencing.

Conclusions: Functional characterisation of the lower airway microbiota through metatranscriptome identify metabolically active organisms capable of producing metabolites with immunomodulatory capacity such as SCFAs.
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http://dx.doi.org/10.1183/13993003.03434-2020DOI Listing
January 2021

Lower Airway Dysbiosis Affects Lung Cancer Progression.

Cancer Discov 2021 Feb 11;11(2):293-307. Epub 2020 Nov 11.

Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, New York.

In lung cancer, enrichment of the lower airway microbiota with oral commensals commonly occurs, and models support that some of these bacteria can trigger host transcriptomic signatures associated with carcinogenesis. Here, we show that this lower airway dysbiotic signature was more prevalent in the stage IIIB-IV tumor-node-metastasis lung cancer group and is associated with poor prognosis, as shown by decreased survival among subjects with early-stage disease (I-IIIA) and worse tumor progression as measured by RECIST scores among subjects with stage IIIB-IV disease. In addition, this lower airway microbiota signature was associated with upregulation of the IL17, PI3K, MAPK, and ERK pathways in airway transcriptome, and we identified as the most abundant taxon driving this association. In a KP lung cancer model, lower airway dysbiosis with led to decreased survival, increased tumor burden, IL17 inflammatory phenotype, and activation of checkpoint inhibitor markers. SIGNIFICANCE: Multiple lines of investigation have shown that the gut microbiota affects host immune response to immunotherapy in cancer. Here, we support that the local airway microbiota modulates the host immune tone in lung cancer, affecting tumor progression and prognosis...
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http://dx.doi.org/10.1158/2159-8290.CD-20-0263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858243PMC
February 2021

Episodic Aspiration with Oral Commensals Induces a MyD88-dependent, Pulmonary Th17 Response that Mitigates Susceptibility to .

Am J Respir Crit Care Med 2020 Nov 9. Epub 2020 Nov 9.

New York University, Pulmonary and Critical Care Medicine, New York, New York, United States;

Rationale Cross-sectional human data suggest that enrichment of oral anaerobic bacteria in the lung is associated with increased Th17 inflammatory phenotype. In this study we evaluated the microbial and host immune response dynamics after aspiration with a oral commensals using a preclinical mouse model. Methods Aspiration with a mixture of human oral commensals (MOC; Prevotella melaninogenica, Veillonella parvula, and Streptococcus mitis) was modeled in mice followed by variable time of sacrifice. Genetic background of mice included WT, MyD88 knock out and STAT3C. Measurements 16S rRNA gene sequencing characterized changes in microbiota. Flow cytometry, cytokine measurement via Luminex and RNA host transcriptome sequencing was used to characterize host immune phenotype. Main Results While MOC aspiration correlated with lower airway dysbiosis that resolved within five days, it induced an extended inflammatory response associated with IL17-producing T-cells lasting at least 14 days. MyD88 expression was required for the IL-17 response to MOC aspiration, but not for T-cell activation or IFN-γ expression. MOC aspiration prior to a respiratory challenge with S. pneumoniae led to a decreased in host's susceptibility to this pathogen. Conclusions Thus, in otherwise healthy mice, a single aspiration event with oral commensals are rapidly cleared from the lower airways, but induce a prolonged Th17 response that secondarily decreased susceptibility to respiratory pathogens. Translationally, these data implicate an immuno-protective role of episodic microaspiration of oral microbes in the regulation of the lung immune phenotype and mitigation of host susceptibility to infection with lower airway pathogens.
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http://dx.doi.org/10.1164/rccm.202005-1596OCDOI Listing
November 2020

Use of exhaled breath condensate (EBC) in the diagnosis of SARS-COV-2 (COVID-19).

Thorax 2021 01 23;76(1):86-88. Epub 2020 Oct 23.

Department of Molecular Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

False negatives from nasopharyngeal swabs (NPS) using reverse transcriptase PCR (RT-PCR) in SARS-CoV-2 are high. Exhaled breath condensate (EBC) contains lower respiratory droplets that may improve detection. We performed EBC RT-PCR for SARS-CoV-2 genes (E, S, N, ORF1ab) on NPS-positive (n=16) and NPS-negative/clinically positive COVID-19 patients (n=15) using two commercial assays. EBC detected SARS-CoV-2 in 93.5% (29/31) using the four genes. Pre-SARS-CoV-2 era controls (n=14) were negative. EBC was positive in NPS negative/clinically positive patients in 66.6% (10/15) using the identical E and S (E/S) gene assay used for NPS, 73.3% (11/15) using the N/ORF1ab assay and 14/15 (93.3%) combined.
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http://dx.doi.org/10.1136/thoraxjnl-2020-215705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590263PMC
January 2021

An integrated multidisciplinary model of COVID-19 recovery care.

Ir J Med Sci 2020 Sep 7. Epub 2020 Sep 7.

Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland.

Background: In January 2020, the WHO declared the SARS-CoV-2 outbreak a public health emergency; by March 11, a pandemic was declared. To date in Ireland, over 3300 patients have been admitted to acute hospitals as a result of infection with COVID-19.

Aims: This article aims to describe the establishment of a COVID Recovery Service, a multidisciplinary service for comprehensive follow-up of patients with a hospital diagnosis of COVID-19 pneumonia.

Methods: A hybrid model of virtual and in-person clinics was established, supported by a multidisciplinary team consisting of respiratory, critical care, infectious diseases, psychiatry, and psychology services. This model identifies patients who need enhanced follow-up following COVID-19 pneumonia and aims to support patients with complications of COVID-19 and those who require integrated community care.

Results: We describe a post-COVID-19 service structure together with detailed protocols for multidisciplinary follow-up. One hundred seventy-four patients were discharged from Beaumont Hospital after COVID-19 pneumonia. Sixty-seven percent were male with a median age (IQR) of 66.5 (51-97). Twenty-two percent were admitted to the ICU for mechanical ventilation, 11% had non-invasive ventilation or high flow oxygen, and 67% did not have specialist respiratory support. Early data suggests that 48% of these patients will require medium to long-term specialist follow-up.

Conclusions: We demonstrate the implementation of an integrated multidisciplinary approach to patients with COVID-19, identifying those with increased physical and mental healthcare needs. Our initial experience suggests that significant physical, psychological, and cognitive impairments may persist despite clinical resolution of the infection.
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http://dx.doi.org/10.1007/s11845-020-02354-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475726PMC
September 2020

Evidence for Environmental-Human Microbiota Transfer at a Manufacturing Facility with Novel Work-related Respiratory Disease.

Am J Respir Crit Care Med 2020 12;202(12):1678-1688

Department of Medicine and.

Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease. As part of a public health investigation of a manufacturing facility, we performed a cross-sectional study using paired environmental and human sampling to evaluate the cross-pollination of microbes between the environment and the host and possible effects on lung pathology present among workers. Workplace environmental microbiota were evaluated in air and MWF samples. Human microbiota were evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, in lung tissue samples from control subjects, and in skin, nasal, and oral samples from 302 workers from different areas of the facility. effects of MWF exposure on murine B cells were assessed. An increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared with control subjects. Among workers in different locations within the facility, those that worked in the machine shop area had skin, nasal, and oral microbiota more closely related to the microbiota present in the MWF samples. Lung samples from four index cases and skin and nasal samples from workers in the machine shop area were enriched with , the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation , a hallmark cell subtype found in the pathology of index cases. Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard.
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http://dx.doi.org/10.1164/rccm.202001-0197OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737585PMC
December 2020

Perspectives in lung microbiome research.

Curr Opin Microbiol 2020 08 2;56:24-29. Epub 2020 Jul 2.

Division of Pulmonary, Critical Care, & Sleep Medicine, Department of Medicine, New York University School of Medicine, NY, United States. Electronic address:

Our understanding of the existence and role of the lung microbiome has grown at a slower pace than other microbiome research areas. This is likely a consequence of the original dogma that the lung was a sterile environment although there are other barriers that are worth discussing. Here we will not be conducting an exhaustive review of the current literature on the lung microbiome, but rather we will focus on what we see as some important challenges that the field needs to face in order to improve our mechanistic understanding of the lung microbiome and its role on human health.
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http://dx.doi.org/10.1016/j.mib.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744389PMC
August 2020

Characterization of the Inflammatory Response to Severe COVID-19 Illness.

Am J Respir Crit Care Med 2020 09;202(6):812-821

Department of Medicine.

Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness. Levels of IL-1β, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVID patients), patients with COVID-19 requiring ICU admission (COVID patients), and patients with severe community-acquired pneumonia requiring ICU support (CAP patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated. IL-1β, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVID patients could be clearly differentiated from COVID patients, and demonstrated higher levels of IL-1β, IL-6, and sTNFR1 but lower IL-10 than CAP patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission ( < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution ( < 0.0001). The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.
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http://dx.doi.org/10.1164/rccm.202005-1583OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491404PMC
September 2020

Sputum neutrophil elastase associates with microbiota and in bronchiectasis.

Eur Respir J 2020 10 22;56(4). Epub 2020 Oct 22.

University of Milan, Dept of Pathophysiology and Transplantation, Milan, Italy.

Introduction: Neutrophilic inflammation is a major driver of bronchiectasis pathophysiology, and neutrophil elastase activity is the most promising biomarker evaluated in sputum to date. How active neutrophil elastase correlates with the lung microbiome in bronchiectasis is still unexplored. We aimed to understand whether active neutrophil elastase is associated with low microbial diversity and distinct microbiome characteristics.

Methods: An observational, cross-sectional study was conducted at the bronchiectasis programme of the Policlinico Hospital in Milan, Italy, where adults with bronchiectasis were enrolled between March 2017 and March 2019. Active neutrophil elastase was measured on sputum collected during stable state, microbiota analysed through 16S rRNA gene sequencing, molecular assessment of respiratory pathogens carried out through real-time PCR and clinical data collected.

Results: Among 185 patients enrolled, decreasing α-diversity, evaluated through the Shannon entropy (ρ -0.37, p<0.00001) and Pielou's evenness (ρ -0.36, p<0.00001) and richness (ρ -0.33, p<0.00001), was significantly correlated with increasing elastase. A significant difference in median levels of Shannon entropy as detected between patients with neutrophil elastase ≥20 µg·mL (median 3.82, interquartile range 2.20-4.96) neutrophil elastase <20 µg·mL (4.88, 3.68-5.80; p<0.0001). A distinct microbiome was found in these two groups, mainly characterised by enrichment with in the high-elastase group and with in the low-elastase group. Further confirmation of the association of with elevated active neutrophil elastase was found based on standard culture and targeted real-time PCR.

Conclusions: High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to infection.
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http://dx.doi.org/10.1183/13993003.00769-2020DOI Listing
October 2020

Personalized Biofeedback on Inhaler Adherence and Technique by Community Pharmacists: A Cluster Randomized Clinical Trial.

J Allergy Clin Immunol Pract 2020 02 27;8(2):635-644. Epub 2019 Sep 27.

Clinical Research Centre, Beaumont Hospital, RCSI, Dublin, Ireland; Department of Respiratory Medicine, RCSI, Dublin, Ireland. Electronic address:

Background: Guidelines recommend that patients treated with inhalers receive adherence counseling and device training. Digital technologies that assess both inhaler adherence and technique have been developed. Using these technologies community pharmacists, who have regular contact with patients, are well placed to deliver personalized inhaler education.

Objective: To determine the impact of a pharmacist intervention, informed by digital technology, on inhaler technique and adherence of patients with asthma in the community.

Methods: A cluster randomized, parallel-group, multisite pharmacy study was conducted over 6 months. All study groups had an electronic device (inhaler compliance assessment device) attached to their maintenance inhaler. A biofeedback group received personalized inhaler training informed by data recorded by the device. The demonstration group received inhaler training, by physical demonstration with a placebo inhaler. The control group received usual care. The primary outcome was inhaler adherence, which was classified as "actual adherence" and expressed as the proportion of expected drug accumulation if adherence and technique had been perfect. Secondary outcomes were quality-of-life scores as measured by the St George's Respiratory Questionnaire, symptoms, and exacerbations.

Results: A total of 152 participants (n = 74 biofeedback, n = 56 demonstration, and n = 22 control) were recruited. Asthma was the predominant condition among participants (n = 83), with chronic obstructive pulmonary disease (n = 55) and asthma/chronic obstructive pulmonary disease overlap also reported (n = 8). In intention-to-treat analysis, adherence in the biofeedback group during month 2 was 62%, 18% higher (95% CI, 6 to 30) than that in the demonstration group (P = .004) and 24% higher (95% CI, 9 to 40) than that in the control group (P = .003). During month 6, adherence was 14% higher (95% CI, -1 to 30; P = .07) in the biofeedback group than in the demonstration group and 31% higher (95% CI, 13 to 48; P = .001) than in the control group. At the end of the study, the biofeedback group had a sustained fall in St George's Respiratory Questionnaire from baseline, -6.1 (95% CI, -9 to -0.4; P = .04) and had significantly improved daily respiratory symptoms.

Conclusions: Community pharmacist-delivered inhaler training informed by a digital technology improved adherence and health status.
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http://dx.doi.org/10.1016/j.jaip.2019.09.008DOI Listing
February 2020

Evaluation of the airway microbiome in nontuberculous mycobacteria disease.

Eur Respir J 2018 10 25;52(4). Epub 2018 Oct 25.

Division of Pulmonary, Critical Care, and Sleep Medicine, New York University School of Medicine, New York, NY, USA.

Aspiration is associated with nontuberculous mycobacterial (NTM) pulmonary disease and airway dysbiosis is associated with increased inflammation. We examined whether NTM disease was associated with a distinct airway microbiota and immune profile.297 oral wash and induced sputum samples were collected from 106 participants with respiratory symptoms and imaging abnormalities compatible with NTM. Lower airway samples were obtained in 20 participants undergoing bronchoscopy. 16S rRNA gene and nested mycobacteriome sequencing approaches characterised microbiota composition. In addition, inflammatory profiles of lower airway samples were examined.The prevalence of NTM cultures was 58%. Few changes were noted in microbiota characteristics or composition in oral wash and sputum samples among groups. Among NTM samples, 27% of the lower airway samples were enriched with A mycobacteriome approach identified in a greater percentage of samples, including some nonpathogenic strains. In NTM lower airway samples, taxa identified as oral commensals were associated with increased inflammatory biomarkers.The 16S rRNA gene sequencing approach is not sensitive in identifying NTM among airway samples that are culture-positive. However, associations between lower airway inflammation and microbiota signatures suggest a potential role for these microbes in the inflammatory process in NTM disease.
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http://dx.doi.org/10.1183/13993003.00810-2018DOI Listing
October 2018

Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation.

Am J Respir Crit Care Med 2019 01;199(1):99-109

1 Division of Pulmonary, Critical Care, and Sleep Medicine, New York University School of Medicine, New York, New York.

Rationale: Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome.

Objectives: To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers.

Methods: Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated.

Measurements And Main Results: In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota.

Conclusions: We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.
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http://dx.doi.org/10.1164/rccm.201801-0119OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353011PMC
January 2019

Personalising adherence-enhancing interventions using a smart inhaler in patients with COPD: an exploratory cost-effectiveness analysis.

NPJ Prim Care Respir Med 2018 06 27;28(1):24. Epub 2018 Jun 27.

Royal College of Surgeons in Ireland, Clinical Research Centre, Smurfit Building Beaumont Hospital, Dublin, Ireland.

Four inhaler adherence clusters have been identified using the INCA audio device in COPD patients: (1) regular use/good technique, (2) regular use/frequent technique errors, (3) irregular use/good technique, and (4) irregular use/frequent technique errors. Their relationship with healthcare utilization and mortality was established, but the cost-effectiveness of adherence-enhancing interventions is unknown. In this exploratory study, we aimed to estimate the potential cost-effectiveness of reaching optimal adherence in the three suboptimal adherence clusters, i.e., a theoretical shift of clusters 2, 3, and 4 to cluster 1. Cost-effectiveness was estimated over a 5-year time horizon using the Irish healthcare payer perspective. We used a previously developed COPD health-economic model that was updated with INCA trial data and Irish national economic and epidemiological data. For each cluster, interventions would result in additional quality-adjusted life years gained at reasonable investment. Cost-effectiveness was most favorable in cluster 3, with possible cost savings of €845/annum/person.
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http://dx.doi.org/10.1038/s41533-018-0092-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021429PMC
June 2018

Airway Microbiota Is Associated with Upregulation of the PI3K Pathway in Lung Cancer.

Am J Respir Crit Care Med 2018 11;198(9):1188-1198

1 Division of Pulmonary and Critical Care Medicine.

Rationale: In lung cancer, upregulation of the PI3K (phosphoinositide 3-kinase) pathway is an early event that contributes to cell proliferation, survival, and tissue invasion. Upregulation of this pathway was recently described as associated with enrichment of the lower airways with bacteria identified as oral commensals.

Objectives: We hypothesize that host-microbe interactions in the lower airways of subjects with lung cancer affect known cancer pathways.

Methods: Airway brushings were collected prospectively from subjects with lung nodules at time of diagnostic bronchoscopy, including 39 subjects with final lung cancer diagnoses and 36 subjects with noncancer diagnoses. In addition, samples from 10 healthy control subjects were included. 16S ribosomal RNA gene amplicon sequencing and paired transcriptome sequencing were performed on all airway samples. In addition, an in vitro model with airway epithelial cells exposed to bacteria/bacterial products was performed.

Measurements And Main Results: The composition of the lower airway transcriptome in the patients with cancer was significantly different from the control subjects, which included up-regulation of ERK (extracellular signal-regulated kinase) and PI3K signaling pathways. The lower airways of patients with lung cancer were enriched for oral taxa (Streptococcus and Veillonella), which was associated with up-regulation of the ERK and PI3K signaling pathways. In vitro exposure of airway epithelial cells to Veillonella, Prevotella, and Streptococcus led to upregulation of these same signaling pathways.

Conclusions: The data presented here show that several transcriptomic signatures previously identified as relevant to lung cancer pathogenesis are associated with enrichment of the lower airway microbiota with oral commensals.
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http://dx.doi.org/10.1164/rccm.201710-2118OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6221574PMC
November 2018

A novel statistical method for assessing effective adherence to medication and calculating optimal drug dosages.

PLoS One 2018 20;13(4):e0195663. Epub 2018 Apr 20.

Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.

Objective: We derive a novel model-based metric for effective adherence to medication, and validate it using data from the INhaler Compliance Assessment device (INCATM). This technique employs dose timing data to estimate the threshold drug concentration needed to maintain optimal health.

Methods: The parameters of the model are optimised against patient outcome data using maximum likelihood methods. The model is fitted and validated by secondary analysis of two independent datasets from two remote-monitoring studies of adherence, conducted through clinical research centres of 5 Irish hospitals. Training data came from a cohort of asthma patients (~ 47,000 samples from 218 patients). Validation data is from a cohort of 204 patients with COPD recorded between 2014 and 2016.

Results: The time above threshold measure is strongly predictive of adverse events (exacerbations) in COPD patients (Odds Ratio of exacerbation = 0.52 per SD increase in adherence, 95% Confidence Interval [0.34-0.79]). This compares well with the best known previous method, the Area Under the dose-time Curve (AUC) (Odds Ratio = 0.69, 95% Confidence Interval [0.48-0.99]). In addition, the fitted value of the dose threshold (0.56 of prescribed dosage) suggests that prescribed doses may be unnecessarily high given good adherence.

Conclusions: The resulting metric accounts for missed doses, dose-timing errors, and errors in inhaler technique, and provides enhanced predictive validity in comparison to previously used measures. In addition, the method allows us to estimate the correct dosage required to achieve the effect of the medication using the patients' own adherence data and outcomes. The adherence score does depend not on sex or other demographic factors suggesting that effective adherence is driven by individual behavioural factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195663PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909911PMC
July 2018

A randomised clinical trial of feedback on inhaler adherence and technique in patients with severe uncontrolled asthma.

Eur Respir J 2018 01 4;51(1). Epub 2018 Jan 4.

Clinical Research Centre, Smurfit Building Beaumont Hospital, RCSI, Dublin, Ireland

In severe asthma, poor control could reflect issues of medication adherence or inhaler technique, or that the condition is refractory. This study aimed to determine if an intervention with (bio)feedback on the features of inhaler use would identify refractory asthma and enhance inhaler technique and adherence.Patients with severe uncontrolled asthma were subjected to a stratified-by-site random block design. The intensive education group received repeated training in inhaler use, adherence and disease management. The intervention group received the same intervention, enhanced by (bio)feedback-guided training. The primary outcome was rate of actual inhaler adherence. Secondary outcomes included a pre-defined assessment of clinical outcome. Outcome assessors were blinded to group allocation. Data were analysed on an intention-to-treat and per-protocol basis.The mean rate of adherence during the third month in the (bio)feedback group (n=111) was higher than that in the enhanced education group (intention-to-treat, n=107; 73% 63%; 95% CI 2.8%-17.6%; p=0.02). By the end of the study, asthma was either stable or improved in 54 patients (38%); uncontrolled, but poorly adherent in 52 (35%); and uncontrolled, but adherent in 40 (27%).Repeated feedback significantly improved inhaler adherence. After a programme of adherence and inhaler technique assessment, only 40 patients (27%) were refractory and adherent, and might therefore need add-on therapy.
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http://dx.doi.org/10.1183/13993003.01126-2017DOI Listing
January 2018

Advances in Audio-Based Systems to Monitor Patient Adherence and Inhaler Drug Delivery.

Chest 2018 03 5;153(3):710-722. Epub 2017 Sep 5.

Trinity Centre for Bioengineering, Trinity College Dublin, The University of Dublin, Dublin, Ireland; School of Engineering, Trinity College Dublin, The University of Dublin, Dublin, Ireland; School of Medicine, Trinity College Dublin, The University of Dublin, Dublin, Ireland.

Hundreds of millions of people worldwide have asthma and COPD. Current medications to control these chronic respiratory diseases can be administered using inhaler devices, such as the pressurized metered dose inhaler and the dry powder inhaler. Provided that they are used as prescribed, inhalers can improve patient clinical outcomes and quality of life. Poor patient inhaler adherence (both time of use and user technique) is, however, a major clinical concern and is associated with poor disease control, increased hospital admissions, and increased mortality rates, particularly in low- and middle-income countries. There are currently limited methods available to health-care professionals to objectively and remotely monitor patient inhaler adherence. This review describes recent sensor-based technologies that use audio-based approaches that show promising opportunities for monitoring inhaler adherence in clinical practice. This review discusses how one form of sensor-based technology, audio-based monitoring systems, can provide clinically pertinent information regarding patient inhaler use over the course of treatment. Audio-based monitoring can provide health-care professionals with quantitative measurements of the drug delivery of inhalers, signifying a clear clinical advantage over other methods of assessment. Furthermore, objective audio-based adherence measures can improve the predictability of patient outcomes to treatment compared with current standard methods of adherence assessment used in clinical practice. Objective feedback on patient inhaler adherence can be used to personalize treatment to the patient, which may enhance precision medicine in the treatment of chronic respiratory diseases.
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http://dx.doi.org/10.1016/j.chest.2017.08.1162DOI Listing
March 2018

Colonisation of Irish patients with chronic obstructive pulmonary disease by and analysis of the pneumococcal vaccine coverage: a non-interventional, observational, prospective cohort study.

BMJ Open 2017 Jul 9;7(7):e013944. Epub 2017 Jul 9.

Department of Clinical Microbiology, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Beaumont Hospital, Beaumont, Dublin, Republic of Ireland.

Objectives: To characterise the pattern of colonisation and serotypes of among patients with chronic obstructive pulmonary disease (COPD) who currently receive the 23-valent pneumococcal polysaccharide vaccine (PPV-23) according to vaccination status, use of antibiotics and steroids. To investigate the prevalence of PPV-23 and 13-valent pneumococcal conjugate vaccine (PCV-13) serotypes within the study cohort.

Design: A non-interventional, observational, prospective cohort study with a 12 -month follow-up period inclusive of quarterly study visits.

Setting: Beaumont Hospital and The Royal College of Surgeons in Ireland Clinical Research Centre, Dublin, Ireland.

Participants: Patients with an established diagnosis of COPD attending a tertiary medical centre.

Primary Outcome Measure: Colonisation rate of in patients with COPD and characterisation of serotypes of with correlation to currently available pneumococcal vaccines. Sputum and oropharyngeal swab samples were collected for the isolation of .

Secondary Outcome Measure: Seasonality of colonisation of and its relationship with the incidence of exacerbations of COPD.

Results: was detected in 16 of 417 samples, a colonisation incident rate of 3.8% and in 11 of 133 (8%) patients at least once during the study. The majority of isolates were identified in spring and were non-vaccine serotypes for either the PPV-23 or PCV-13 (63%). The colonisation incident rate of fluctuated over the four seasons with a peak of 6.6% in spring and the lowest rate of 2.2% occurring during winter. Antibiotic use was highest during periods of low colonisation.

Conclusions: There is seasonal variation in colonisation among patients with COPD which may reflect antibiotic use in autumn and winter. The predominance of non-vaccine types suggests that PCV-13 may have limited impact among patients with COPD in Ireland who currently receive PPV-23.

Trial Registration Number: NCT02535546; post-results.
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http://dx.doi.org/10.1136/bmjopen-2016-013944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541633PMC
July 2017

In patients with severe uncontrolled asthma, does knowledge of adherence and inhaler technique using electronic monitoring improve clinical decision making? A protocol for a randomised controlled trial.

BMJ Open 2017 06 15;7(6):e015367. Epub 2017 Jun 15.

Department of Medicine, RCSI, Dublin, Ireland.

Introduction: Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes.

Methods And Analysis: This prospective, randomised, multicentre study will compare the impact of using information on adherence to influence asthma treatment. Patients with severe uncontrolled asthma will be included. Data on adherence, inhaler technique and electronically recorded peak expiratory flow rate will be used to promote adherence and guide a clinical decision protocol to guide management in the active group. The control group will receive standard inhaler and adherence education. Medications will be adjusted using a protocol based on Global Initiativefor Asthma (GINA) recommendations. The primary outcome is the between-group difference in the proportion of patients who have refractory disease and are prescribed appropriate medications at the end of 32 weeks. A co-primary outcome is the difference between groups in the rate of adherence to salmeterol/fluticasone inhaler over the last 12 weeks. Secondary outcomes include changes in symptoms, lung function, type-2 cytokine biomarkers and clinical outcomes between both groups. Cost-effectiveness and cost-utility analyses of the INCA device intervention will be performed. The economic impact of a national implementation of the INCA-SUN programme will be evaluated.

Ethics And Dissemination: The results of the study will be published as a manuscript in peer-reviewed journals. The study has been approved by the ethics committees in the five participating hospitals.

Trial Registration: NCT02307669; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2016-015367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734350PMC
June 2017

The Impact of Common Inhaler Errors on Drug Delivery: Investigating Critical Errors with a Dry Powder Inhaler.

J Aerosol Med Pulm Drug Deliv 2017 Aug 9;30(4):247-255. Epub 2017 Mar 9.

1 Clinical Research Centre, Royal College of Surgeons in Ireland , Dublin, Ireland .

Background: Researchers, using checklists, have identified that 30%-90% of patients make errors in inhaler use. It is not certain whether these errors affect the delivery of medication. We have developed an electronic monitor (INCA™) that records audio each time an inhaler is used, providing objective information on inhaler technique. The aim of this study was to assess the effect that correctly identified inhaler errors, with the INCA device, have on drug delivery.

Methods: This was a prospective study of healthy volunteers using a salbutamol Diskus™. The inclusion criteria allowed for the recruitment of healthy participants who were nonfrequent users of Salbutamol. Each participant was assigned to one control "phase" first and two/three subsequent error "phases." Each phase consisted of six doses of the drug taken 6 hours apart, and the participants' blood was drawn before and 25 minutes after doses one and six. This allowed us to sample their trough and peak serum salbutamol levels.

Results: Fourteen healthy volunteers were studied. The inhaler technique errors simulated in this study included exhaling into the device after drug priming but before inhalation, low inspiratory flow, multiple inhalations, low breath hold, missed doses, and wrong inhaler position. Only the exhalation error, low inspiratory flow, and missed doses led to a significant reduction in serum salbutamol levels. After six doses of the exhalation error, there was a 62% reduction in peak salbutamol levels. Low inspiratory flow led to a 52% reduction in peak salbutamol levels and a 78% reduction in trough levels. Missed doses led to a 37% reduction in trough salbutamol levels.

Conclusions: These findings confirm that technique errors affect drug delivery. Furthermore, we were able to identify that the most critical technique errors with the Diskus inhaler are exhalation into the device before inhalation, poor inspiratory flow, and missing doses.
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http://dx.doi.org/10.1089/jamp.2016.1334DOI Listing
August 2017

The INCA (Inhaler Compliance Assessment): A comparison with established measures of adherence.

Psychol Health 2017 Oct 28;32(10):1266-1287. Epub 2017 Feb 28.

a Department of Psychology, Division of Population Sciences , Royal College of Surgeons in Ireland , Dublin , Ireland.

Objective: To compare the Inhaler Compliance Assessment (INCA), a novel audio-recording device objectively measuring timing and proficiency of inhaler use, against established adherence measures, and explore its discriminant and predictive validity.

Design: Prospective observational study; 184 chronic obstructive pulmonary disease (COPD) patients used an INCA-enabled salmeterol/fluticasone inhaler for one-month post-hospital discharge.

Main Outcome Measures: INCA (Attempted, Attempted Interval, Actual) adherence correlated with Doses Used Rate, self-reported adherence and prescription refill for concurrent validity. Discriminant validity for reason for admission, cognition and lung function; predictive validity for health status and quality-of-life.

Results: Rates of Attempted, Attempted Interval and Actual adherence were 59, 47 and 23%, respectively. Only 7% of participants had Actual adherence >80%. INCA variables significantly correlated with Doses Used Rate but not with self-report; Attempted and Attempted Interval were weakly associated with prescription refill. Higher cognitive and lung functioning groups had better INCA adherence. Attempted and Attempted Interval predicted health status, while Doses Used Rate predicted quality-of-life.

Conclusion: INCA did not strongly correlate with self-report or prescription refill data. Discriminant and predictive validity demonstrated by INCA suggests the potential utility of the INCA as a method to identify intentional and unintentional adherence to inhaled medication and facilitate targeted intervention.
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http://dx.doi.org/10.1080/08870446.2017.1290243DOI Listing
October 2017

Changes in inhaler inhalation acoustic features during induced bronchoconstriction: a pilot study.

Annu Int Conf IEEE Eng Med Biol Soc 2016 Aug;2016:3749-3752

Asthma is a chronic respiratory disease affecting millions of people worldwide, and is consequently a major issue for global health. Exacerbations are acute events involving the worsening of asthma's primary respiratory symptoms and are a major cause of morbidity in asthma patients, largely due to the unpredictability of their onset. This study aimed to investigate the relationship between changes in acoustic features of inhaler inhalations and changes in forced expiratory volume in one second (FEV1) that occur during a simulated exacerbation, a bronchial challenge test (BCT). This is a clinical test that simulates an asthma exacerbation through the administration of a bronchoconstrictor agent. Eight patients indicated for a BCT were recruited for this study. Non-contact and tracheal microphones were employed to record Diskus™ inhaler inhalations throughout the course of a BCT. A spirometer was employed to measure inhaler peak inspiratory flow rate (PIFR). In patients responsive to the BCT (n=4), significant correlations between changes in FEV1 and acoustic features on both microphones existed, with fractal increment of Katz fractal dimension yielding the strongest correlation (R=0.58), and between FEV1 and PIFR (R=0.62). These findings suggest that inhaler inhalation acoustic features may assist in the early detection of exacerbations. Future research will determine whether this is the case in a larger cohort of patients with non-simulated exacerbations.
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http://dx.doi.org/10.1109/EMBC.2016.7591543DOI Listing
August 2016

A pilot study to monitor changes in spirometry and lung volume, following an exacerbation of Chronic Obstructive Pulmonary Disease (COPD), as part of a supported discharge program.

Respir Med 2016 10 24;119:55-62. Epub 2016 Aug 24.

Department of Respiratory Medicine, Beaumont Hospital, Dublin, Ireland.

Background: One-third of patients with an exacerbation of Chronic Obstructive Pulmonary Disease(COPD) are re-hospitalised at 90 days. Exacerbation recovery is associated with reductions in lung hyperinflation and improvements in symptoms and physical activity. We assessed the feasibility of monitoring these clinical parameters in the home. We hypothesised that the degree of change in spirometry and lung volumes differs between those who had an uneventful recovery and those who experienced a further exacerbation.

Methods: Hospitalised patients with an acute exacerbation of COPD referred for a supported discharge program participated in the study. Spirometry and Inspiratory Vital Capacity(IVC) were measured in the home at Days 1, 14 and 42 post-discharge. Patients also completed Medical Research Council(MRC), Borg and COPD Assessment Test(CAT) scores and were provided with a tri-axial accelerometer. Any new exacerbation events were recorded.

Results: Sixty-five patients with 72 exacerbation episodes were recruited. Fifty percent experienced a second exacerbation. Adequate IVC measurements were achieved by 90%, while only 70% completed spirometry. Uneventful recovery was accompanied by significant improvements in physiological measurements at day14, improved symptom scores and step count, p < 0.05. Failure of MRC to improve was predictive of re-exacerbation(Area Under Receiver Operating Curve(AUROC) 0.6713) with improvements in FEV≥100 ml(AUROC 0.6613) and mean daily step count ≥396 steps(AUROC 0.6381) predictive of recovery.

Conclusion: Monitoring the pattern of improvement in spirometry, lung volumes, symptoms and step count following a COPD exacerbation may help to identify patients at risk of re-exacerbation. It is feasible to carry out these assessments in the home as part of a supported discharge programme.
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http://dx.doi.org/10.1016/j.rmed.2016.08.019DOI Listing
October 2016

Irregular and Ineffective: A Quantitative Observational Study of the Time and Technique of Inhaler Use.

J Allergy Clin Immunol Pract 2016 Sep-Oct;4(5):900-909.e2

Department of Medicine, Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland; Respiratory Department, Clinical Research Centre, RCSI, Dublin, Ireland.

Background: Cross-sectional observational studies suggest that between 50% and 60% of patients misuse a dry powder inhaler, whereas studies with electronic monitors indicate that patients sometimes overuse/underuse their inhalers. It is not known what impact errors and erratic use have on inhaler adherence.

Objectives: The purpose of this study was to longitudinally quantify when and how patients adhered to a twice-daily preventer treatment by using a novel acoustic recording device attached to an inhaler (INhaler Compliance Assessment).

Methods: Patients with a history of asthma or chronic obstructive pulmonary disease (n = 123) from primary care and community pharmacies were given an INhaler Compliance Assessment-adapted inhaler for 1 month. Analysis of the audio files provided quantitative information on time and technique of inhaler use.

Results: Data were available for 103 patients. Twenty-one patients (20%) used their inhaler in the correct manner at the correct interval. There were 5045 audio files with attempted inhalations, of which 1204 had technique errors (24%). Errors included inadequate flow (27%), drug priming without inhalation (19%), exhalation into the inhaler (18%), and multiple inhalations (25%). On average, participants made errors 20% of the time. Of 60 doses expected to be taken in a month per person, on average 49 doses (82%) were attempted and when errors were accounted for, the average number of actual doses taken was 34 doses (57%; P < .01) comparing attempted to actual doses.

Discussion: These data highlight that ineffective and irregular inhaler use is common and when combined in a single calculation indicate that only 20% of participants used their inhaler correctly and on time.
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http://dx.doi.org/10.1016/j.jaip.2016.07.009DOI Listing
October 2017

A Method to Calculate Adherence to Inhaled Therapy that Reflects the Changes in Clinical Features of Asthma.

Ann Am Thorac Soc 2016 11;13(11):1894-1903

1 Department of Respiratory Medicine.

Rationale: Currently, studies on adherence to inhaled medications report average adherence over time. This measure does not account for variations in the interval between doses, nor for errors in inhaler use.

Objectives: To investigate whether adherence calculated as a single area under the (concentration-time) curve (AUC) measure, incorporating the interval between doses and inhaler technique, was more reflective of patient outcomes than were current methods of assessing adherence.

Methods: We attached a digital audio device (INhaler Compliance Assessment) to a dry powder inhaler. This recorded when the inhaler was used, and analysis of the audio data indicated if the inhaler had been used correctly. These aspects of inhaler use were combined to calculate adherence over time, as an AUC measure. Over a 3-month period, a cohort of patients with asthma was studied. Adherence to a twice-daily inhaler preventer therapy using this device and clinical measures were assessed.

Measurements And Main Results: Recordings from 239 patients with severe asthma were analyzed. Average adherence that was based on the dose counter was 84.4%, whereas the ratio of expected to observed accumulated AUC, actual adherence, was 61.8% (P < 0.01). Of all the adherence measures, only adherence calculated as AUC reflected changes in asthma quality of life, β-agonist reliever use, and peak expiratory flow over the 3 months (P < 0.05 compared with other measures of adherence).

Conclusions: Adherence that incorporates the interval between doses and inhaler technique, and calculated as AUC, is more reflective of changes in quality of life and lung function than are the currently used measures of adherence. Clinical trial registered with www.clinicaltrials.gov (NCT 01529697).
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http://dx.doi.org/10.1513/AnnalsATS.201603-222OCDOI Listing
November 2016

Objective Assessment of Adherence to Inhalers by Patients with Chronic Obstructive Pulmonary Disease.

Am J Respir Crit Care Med 2017 05;195(10):1333-1343

1 Clinical Research Centre, Beaumont Hospital.

Rationale: Objective adherence to inhaled therapy by patients with chronic obstructive pulmonary disease (COPD) has not been reported.

Objectives: To objectively quantify adherence to preventer Diskus inhaler therapy by patients with COPD with an electronic audio recording device (INCA).

Methods: This was a prospective observational study. On discharge from hospital patients were given a salmeterol/fluticasone inhaler with an INCA device attached. Analysis of this audio quantified the frequency and proficiency of inhaler use.

Measurements And Main Results: Patients with COPD (n = 244) were recruited. The mean age was 71 years, mean FEV was 1.3 L, and 59% had evidence of mild/moderate cognitive impairment. By combining time of use, interval between doses, and critical technique errors, thus incorporating both intentional and unintentional nonadherence, a measure "actual adherence" was calculated. Mean actual adherence was 22.6% of that expected if the doses were taken correctly and on time. Six percent had an actual adherence greater than 80%. Hierarchical clustering found three equally sized well-separated clusters corresponding to distinct patterns. Cluster 1 (34%) had low inhaler use and high error rates. Cluster 2 (25%) had high inhaler use and high error rates. Cluster 3 (36%) had overall good adherence. Poor lung function and comorbidities were predictive of poor technique, whereas age and cognition with poor lung function distinguished those with poor adherence and frequent errors in technique.

Conclusions: These data may inform clinicians in understanding why a prescribed inhaler is not effective and to devise strategies to promote adherence in COPD.
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http://dx.doi.org/10.1164/rccm.201604-0733OCDOI Listing
May 2017

Predicting asthma exacerbations employing remotely monitored adherence.

Healthc Technol Lett 2016 Mar 23;3(1):51-5. Epub 2016 Mar 23.

Clinical Research Centre, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland; Department of Medicine, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin, Ireland.

This Letter investigated the efficacy of a decision-support system, designed for respiratory medicine, at predicting asthma exacerbations in a multi-site longitudinal randomised control trial. Adherence to inhaler medication was acquired over 3 months from patients with asthma employing a dose counter and a remote monitoring adherence device which recorded participant's inhaler use: n = 184 (23,656 audio files), 61% women, age (mean ± sd) 49.3 ± 16.4. Data on occurrence of exacerbations was collected at three clinical visits, 1 month apart. The relative risk of an asthma exacerbation for those with good and poor adherence was examined employing a univariate and multivariate modified Poisson regression approach; adjusting for age, gender and body mass index. For all months dose counter adherence was significantly (p < 0.01) higher than remote monitoring adherence. Overall, those with poor adherence had a 1.38 ± 0.34 and 1.42 ± 0.39 (remotely monitored) and 1.25 ± 0.32 and 1.18 ± 0.31 (dose counter) higher relative risk of an exacerbation in model 1 and model 2, respectively. However, this was not found to be statistically significantly different. Remotely monitored adherence holds important clinical information and future research should focus on refining adherence and exacerbation measures. Decision-support systems based on remote monitoring may enhance patient-physician communication, possibly reducing preventable adverse events.
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http://dx.doi.org/10.1049/htl.2015.0058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814807PMC
March 2016

High prevalence of obstructive lung disease in non-smoking farmers: The Irish farmers lung health study.

Respir Med 2016 06 20;115:13-9. Epub 2016 Apr 20.

Department of Respiratory Medicine, Galway University Hospital, Galway, Ireland.

Background: Mortality rates within the Irish farming community are increasing, whilst that of the general population falls. The aim of this cross-sectional study was to determine the prevalence of respiratory disease amongst Irish farmers.

Methods: All study participants were farming volunteers attending an agricultural exhibition. Data collected by questionnaire included baseline demographics, respiratory history, presence of respiratory symptoms and occupational exposures. Spirometry was performed on all participants.

Results: Data from 372 farmers was analysed. The majority were male (76%) with median age of 55 years. 61% were never smokers. 13% were previously diagnosed with airway disease (Chronic Obstructive Pulmonary Disease(COPD)/Asthma/Inhaler use) with 14% reporting hayfever/allergies. Almost two-thirds reported one or more chronic respiratory symptom. Forty-four (12%) had obstructive spirometry using fixed FEV1/FVC < 0.70 criterion and 29 (7.8%) using FEV1/FVC < 5% lower limit of normal. The majority, two-thirds, were never smokers. Amongst never smokers with obstruction (13%), there was a significantly higher proportion with a prior diagnosis of airway disease and hayfever/allergies. There was no significant association between specific occupational exposures and obstruction.

Conclusion: The majority of Irish farmers are never smokers. They have a high prevalence of respiratory symptoms. 13% of never smokers have airflow obstruction (FEV1/FVC < 0.70). The presence of airflow obstruction is significantly associated with self-reported allergy history and prior airway disease. Further studies are needed to identify the workplace factors accounting for these findings.
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http://dx.doi.org/10.1016/j.rmed.2016.04.006DOI Listing
June 2016