The Big Impact Infection: NTM MAC
The clinical implications of infection
Non-tuberculous mycobacteria pulmonary disease (NTM-PD) often leads to a patient’s health-related quality of life being reduced, time spent in hospital being increased and length of life being potentially shortened. Testing rates for NTM-PD are variable but usually low and adherence to guideline based therapy is poor. For a disease which has so many consequences, why isn’t more being done?
NTM are naturally occurring opportunistic pathogens which can cause infections in various different body sites. Whilst the lung is the most common site of NTM infection, lymph nodes, soft tissue, skin and blood can also be involved.1 2 When NTM persistently colonises the lungs, it is referred to as NTM pulmonary disease (NTM-PD),3 the incidence of which is increasing globally.4 5
The symptoms of an infection caused by NTM are often non-specific and mirror those of underlying diseases, complicating diagnosis.6 7 8 For example, symptoms of NTM-PD include cough, shortness of breath, sputum production, coughing up blood, wheezing and chest pain.1 9 10 11
Although there are no quality of life tools that have been developed specifically for patients with NTM-PD,3 it does often reduce patients’ health-related quality of life.12 A generic health related quality of life instrument, SF-36, demonstrated that scores for physical functioning, role physical, general health perceptions, social functioning bodily pain and energy were all lower than the expected value of 50 in patients with NTM-PD.12
Not only can health-related quality of life be significantly impacted when living with NTM-PD, but length of life is often shortened, with patients having twice the rate of all-cause mortality compared with matched controls.12 13 14 15 16 Furthermore, mortality rates are particularly high for COPD patients with NTM-PD compared to those without NTM-PD, being 41.5% and 15.9% respectively.17
Daily life can be challenging enough for those living with NTM-PD, without the worry of unexpected hospital admissions. However, NTM-PD places patients at an increased risk of hospitalisations, experiencing nearly six times more all cause secondary care events. For patients presenting with both NTM-PD and chronic respiratory disease, a threefold higher secondary care utilisation is observed, compared to those without NTM-PD.18 19 20
Not only is NTM-PD potentially crippling for the patients living with it, but the entire healthcare system also suffers - the mean direct healthcare expenditure for an NTM-PD patient has been shown to be nearly four times that of a matched control (matched by age, sex and Charlson Comorbidity Index).17
Of all the species of NTM capable of causing pulmonary infection, Mycobacterium avium complex (MAC) is one of the most common.21 Between 2007 and 2012, 35.6% of culture positive pulmonary NTM isolates were found to be MAC.22 And at one particular hospital in England, MAC was shown to be responsible for, on average, 43% of all NTM isolates between 2000 and 2014 and up to a maximum of 52%.23
The outcomes associated with NTM MAC pulmonary disease are particularly poor, having an overall 10 year all-cause mortality of 46.5%.24 There are two presentations of MAC pulmonary disease – fibrocavitary, the traditionally recognised presentation of MAC pulmonary disease, and nodular bronchiectatic.
Fibrocavitary MAC pulmonary disease is characterised by fibrosis or cavity formation in the lungs, particularly the upper lobes. Fibrocavitary MAC pulmonary disease is generally progressive within a relatively short time frame and, if left untreated, can result in extensive cavitary lung destruction and respiratory failure.6 Radiological outcomes for patients with cavitary MAC pulmonary disease have been shown to be worse compared to those who have non-cavitary disease. In 536 patients with nodular bronchiectatic MAC pulmonary disease, at 5 years following diagnosis, 34.6% of those with non-cavitary disease showed radiographic deterioration compared to 66.7% of those with cavitary disease. These percentages increase to 51.7% and 70.4% respectively at 10 years following diagnosis.25
Nodular bronchiectasis, on the other hand is characterised by accumulation of pus, blood and nutrient rich fluid in the lungs, particularly in the right middle lobe or the lingula.6 9 A recent study involving 40 patients with untreated nodular bronchiectatic MAC pulmonary disease demonstrated that 97.5% of patients showed radiologic deterioration on serial chest CT scans over long-term observation periods.26
Patients with persistent culture positive MAC pulmonary disease show increased rates of radiographic progression. A study investigating 126 patients with MAC pulmonary disease found that 54% of patients with persistent culture positivity experienced radiographic progression as against 30% with negative culture.27 Furthermore, NTM MAC pulmonary disease can have a devastating impact on patients, with all aspects of normal daily life potentially being affected.