Risk factors and secondary care utilisation in a primary care population with non-tuberculous mycobacterial disease in the UK

Abstract

Prior research has identified risk factors associated with developing non-tuberculous mycobacterial disease (NTMD); we identified risk factors and secondary care utilisation of NTMD patients in the UK. This was a matched case-control study using electronic healthcare records from Clinical Practice Research Datalink from 2006 to 2016. NTMD was defined using prescription data and Read codes, based on international guidelines. Risk factors for NTMD were investigated using conditional logistic regression within a representative general population. All-cause secondary care utilisation (combined inpatient, outpatient, emergency visits) was investigated for participants with linked Hospital Episode Statistics (HES), using incidence rate ratio (IRR) from 2007 to 2015. We identified 1225 individuals with NTMD. A subset of individuals (426 patients) were eligible for linkage with HES. In the adjusted model, risk factors most strongly associated with an increased likelihood of NTMD included previous tuberculosis (OR 69.0; 47.7–99.8); bronchiectasis (OR 23.3; 12.4–43.9); lung cancer (OR 14.9; 3.98–55.7); oral corticosteroids (OCS; OR 7.28; 4.94–10.7); immunosuppressive (excluding corticosteroids) medication (OR 3.05; 1.15–8.10); being underweight (odds ratio (OR) 2.92; 95% CI 1.95, 4.36); and rheumatoid arthritis (OR 2.12; 1.05–4.27). NTMD patients had significantly higher rates of all-cause secondary care utilisation than non-NTMD patients (IRR 5.80; 5.14–6.46). Using a representative adult population, we identified prior TB, bronchiectasis, lung cancer, immunosuppressive medication, and OCS as the risk factors associated with the highest odds of developing NTMD in the UK. Patients with NTMD experienced nearly six times more all-cause secondary care events following their NTMD diagnosis than patients without NTMD.

The Rise of Non-Tuberculosis Mycobacterial Lung Disease

“…Over the last decades it has become apparent that several groups of individuals are prone to PNTM disease (Figure 1). These include patients with both genetic or acquired structural lung diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, alpha-1 antitrypsin deficiency, previous pulmonary tuberculosis, and lung cancer (16)(17)(18). Patients with immune suppression due to primary immune deficiency syndromes (PIDs) such as Mendelian Susceptibility to Mycobacterial Disease (MSMD) associated with IL12-p40, IL12, IFNγ receptor abnormalities and gene deformities (IFNγR1, IFNγR2, IL12RB1, IL12B, STAT1, IKBKG, CYBB, ISG15, IRF8, GATA2) are at high risk of NTM infection (19)(20)(21).…”

“…A multicentre study of MAC infection across Canada, France, Germany and the UK conducted in 2018 showed average direct medical costs per person year ranged from $US12,200 in Canada to $US25,500 in France (71). In addition to direct disease related costs, patients were also shown to have six times higher secondary care utilization events for disease-related and disease-unrelated illnesses (18).…”

“…However, no consistent phenotype of immune protection or immune susceptibility has been described. Immune compromise caused by genetic mutations (MSMD) and acquired defects due to infections like HIV usually lead to disseminated infection while iatrogenic causes (inhaled or systemic corticosteroids, anti-TNF therapy, chemotherapeutic agents), and defects in lung structural and functional integrity (primary ciliary dyskinesia and other mutations leading to ciliary dysfunction, CFTR mutations, bronchiectasis, COPD, α1 antitrypsin deficiency, lung malignancy, and ATT) and pulmonary alveolar proteinosis, are known predispositions to pulmonary NTM disease (18,22,82). Previous or concomitant TB infection and Aspergillosis independently increase risk of PNTM (83).…”

Nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex - disease burden, unmet needs, and advances in treatment developments

“…Risk of NTM-LD is also increased in the elderly [38]. A history of pulmonary TB has also been reported as an important risk factor for NTM-LD in countries such as France, Denmark and the UK [39][40][41], as well as in regions with high prevalence of pulmonary TB [27][28][29]. There is no evidence of human-to-human transmission of MAC.…”

Current and future management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) in the UK

“…Open access box 1 Factors which increase the risk of developing non-tuberculous mycobacterial pulmonary disease [12][13][14][15][16][17][18][19][20][21] ► Alcohol misuse ► Biological agents ► Chronic kidney disease ► Diabetes ► Female gender ► Gastro-oesophageal reflux disease ► Immunocompromise, primary or secondary to disease or drug therapies ► Inhaled corticosteroids ► Low body mass index ► Pneumoconiosis ► Underlying structural lung disease, for example, bronchiectasis, and COPD (chronic obstructive pulmonary disease) gastro-oesophageal reflux disease (GORD). Chest X-rays carried out by the COPD team look generally similar to previous imaging, though occasional nodularity that appeared to resolve on repeat imaging was noted.…”