Table 2.

Factors associated with PNTM

Related to	Factor	Comments
Host	a) Structural lung defects	• COPD [45–52] • Bronchiectasis [53–56]  • Post TB infection [57–60]  • Cystic fibrosis [61–66]  • ABPA [67–73]  • Impaired mucociliary clearance [74–77]
	b) Genetic defects	• Genetic defects in genes related with immune response, CFTR, cilia, and connective tissue [74, 78–83]
	c) Immunodeficiencies	Primary immunodeficiency • Gene mutations [84–109]
		Secondary immunodeficiencies • HIV [110–119] • Autoimmune diseases [120] • Cancer [121–123] • Immunosuppressive drugs [124–129] • Surgery [130–133] o Transplantation [134–138] • Age over 60 years old/Immunosenescence [139–151] • Malnutrition [152–161] • Vitamin and trace elements deficiencies [162–175] • Addictions: smoking, alcoholism, and drug abuse [176–203] • Lady/Lord Windermere syndrome [204–208]
NTM	a) Virulence factors	• Genomic and proteomic analyses identified virulence genes and proteins in NTM similar to Mtb [209–212] • Cell wall components related to virulence, immunogenicity, immunomodulation and drug sensitivity [213–222]
	b) Biofilm	• Resistance to physiochemical stress, antimicrobials and immune defence mechanisms [20–26, 223–229]
	Transmission
	a) Water	• Global warming increase water evaporation and aerosolization of NTM on water surface [230–238] • Insufficient treatment of water to avoid NTM colonization [239–241] • Showering, hot bath, sauna and swimming pools increase exposure to PNTM infection [242–244]
	b) Soil and dust particles	• High exposure to aerosolized dust/soil in construction, industrial / domestic / recreational activities associated with improper use of personal protective equipment [230, 245–250]
	c) Other sources	• Natural disasters, armed conflicts, terrorist attacks and migrations related to poor health conditions [233, 245, 251, 252] • Spread of disease due to ease of transportation [234–236]
Control of PNTM	A. Prophylaxis
	a) NTM (Blocking the transmission)	• Avoid aerosolization [41, 253, 254] • Use of personal protective equipment [255]
	b) Host (Vaccines)	• Need to increase research on vaccine development for PNTM [43] • Experimental and clinical results of mycobacterial vaccines support further development in this area [256–278]
	B. Management of the disease
	a) Diagnosis	• Mainly focussed on TB, and little development for NTM [43, 279–290]
	b) Treatment	• Need to develop new effective drugs for NTM [43, 44]
		Immunotherapy • Potential use of monoclonal antibodies specific of NTM antigens and/or human IgG or IgA formulations and therapeutic vaccines [256–278, 291–314]
	c) Drug discovery	• Multiple challenges in discovery and development of new antibiotics for NTM [315–326]