Table 6.

Implications of related subclinical physiological changes that are observed in relation to WP smoking in adolescents and young adults for chronic disease pathology

Outcome measures	Implication/meaning
Alteration of saliva biochemistry	Changes in the acidity (pH) and ability to buffer against it in the saliva can cause loss of enamel, increase potential for infection and disease (e.g. oral thrush). Alteration of background microorganism composition (microbiome) in the oral cavity as observed for WP may increase the risk of infection18,19.
Spirometry or lung function	Decline in lung function was often associated with WP smoking in the studies. Rapid (non-age related) decline in lung function (volume capacity and air flow from the lungs) is involved in the pathogenesis of respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer39.
Cellular composition in small airway epithelium	The decrease in ciliated cells and increase in mucous secreting cells in small airway epithelium degrades the lung clearance mechanism. Such alterations can be caused by exogenous insults, were observed in relation to WP smoking, and do occur during the development of chronic respiratory diseases33.
Hematological parameters	WP increased hematological parameters including hematocrit (proportion of red blood cells in the blood) and white blood cell counts. Chronic changes in these parameters alter cardiovascular function and may contribute to or indicate disease84.
Hemodynamic measurements	Measures of blood flow dynamics including BP are altered by WP smoking. An overly elevated BP (hypertension) or reduced BP (hypotension) may precipitate or indicate chronic diseases including in the cardiovascular system63.
Vascular function measures	Measures of vascular function including FMD, arterial stiffness, and pulse wave velocity indicate the stiffness and reactivity of blood vessels. Changes in vascular function is an early indicator of atherosclerotic cardiovascular disease and is induced by WP smoking59,76.
Cardiac autonomic control	Change in the autonomic control of cardiovascular function is a predictor of coronary heart disease and mortality and is induced by WP smoking60,77.
Brain-derived neurotrophic factor ( BDNF )	BDNF is involved in brain function and homeostasis. Reduced circulating BDNF concentration in the blood was observed in association with WP smoking and may result in cognitive and behavioral deficit in the long-term87.
Genotoxicity	This includes damage to the structure of the DNA and chromosomes. Genotoxicity initiates the cancer mechanism and its continuous induction by exogenous insults, similar to the observations for WP, can overwhelm cellular defence mechanisms and increase cancer risk21,25.
Epigenetic modification	These are modifications on the DNA or histone that do not change the DNA sequence. They may affect gene transcription and associated expression (production) of protein. Deleterious epigenetic changes, such as was observed in relation to WP smoking, adversely alter cellular metabolism and are often involved in the pathogenesis of chronic diseases including cancer and COPD32,33.
Oxidative stress and inflammatory measures	Oxidative stress (imbalance between production of oxidant species and antioxidant defences in the body) and inflammation (triggering of the immune response) are involved in the pathogenesis of chronic inflammatory diseases (e.g. cardiovascular disease, COPD, and cancer) and are both induced by WP smoking.