Abstract
Question
There is an increasing prevalence of nontuberculous mycobacteria pulmonary disease
(NTM-PD) in the US. Treatment of NTM-PD typically requires multiple medications, which
can be associated with unpleasant morbidity and eradication of infection is difficult.
Therefore, there is a critical need for novel effective and well-tolerated therapies.
Recent in vitro data and case reports have suggested that nitric oxide, inhaled as
a gas (gNO), has antimicrobial activity against NTM. We sought to investigate the
effect of gNO in patients with NTM-PD in an open-label proof of concept trial.
Methods
Eligible participants had NTM-PD with persistently positive respiratory cultures for
NTM even if on antibiotic treatment. Participants were treated with gNO for 50 min
three times daily, five days per week, for three weeks (total of 15 treatment days).
Results
Ten participants, of whom nine were on long-term NTM antibiotic therapy, were enrolled.
All participants completed the regimen without interruption or discontinuation. Small
increases in methemoglobin were noted during treatment, and all resolved to baseline
within 2 h. Four participants (40%) met the primary outcome measure of negative sputum
cultures after three weeks of therapy. Following treatment discontinuation, three
of these participants were again culture positive during the 3-month post-treatment
monitoring period, although with measures suggesting low bacterial burden.
Answer
Patients tolerated a 3-week regimen of gNO without safety concerns, and despite highly
refractory disease four individuals completed the study with negative cultures, although
three were again positive in subsequent months. These data support further investigation
of gNO as a potential therapy for NTM-PD.
Keywords
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Article info
Publication history
Published online: December 01, 2022
Accepted:
November 30,
2022
Received:
July 14,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
