Objective: In this study the main aspects of influenza transmission via fine and ultrafine bioaerosols were considered. Here, we aimed to estimate the impact of the different environment conditions on the deposition rate of the infectious bioaerosols in the respiratory tract. Background: The latest researches show the infected people generate the fine and ultrafine infectious bioaerosols with submicron particles/droplets (size below 1 µm). The airborne transmission of these particles/droplets in the environment is effective. It is considered the deposition of submicron particles in the respiratory tract (RT) has very low probability. But most studies examined the aerosol deposition in RT under normal environmental conditions and did not paid attention to the affecting the different environmental factors. Methods: We review the problems of epidemiology of respiratory infections and aspects of airborne transmission/spread of infectious agents. We contrast these approaches with known data from next areas: inhalation toxicology, respiratory drug delivery and physics of heat and mass transfer in the airways. Results: Based on the conducted analysis, we propose the next main concepts: 1 Breathing cool air leads to the supersaturation of air in RT; 2 the air supersaturation leads to the intensive condensational growth(CG) of inhaled viruses or bacteria in RT; 3 CG leads to the intensive and dramatically growth of deposition rate of viruses or bacteria in RT. We have shown: a) Under normal conditions of inhaled air (T>20˚C; Relatively Humidity, RH=60%) there is no transition in supersaturated condition in RT and CG is insignificant and probability of virus deposition on epithelium of RT is low – no more than 20%. b) Breathing cool/cold air of T<+15˚C and RH of [30..60]% leads to the supersaturation in the airways and it can dramatically increase the deposition rate of inhaled bioaerosols in RT(up to 96%). c) With an increase in RH of inhaled air the supersaturation in RT occurs even at warm temperature of inhaled air (for inhaled air of T<20°C and RH>70% ; T<25°C and RH>90%). Which also indicates the deposition rate of bioaerosols in RT under these conditions is high. Conclusion: Under specific environmental conditions (when flu seasons) the processes of supersaturation in the RT can be observed. These results indicate the high probability of virus deposition on epithelium of RT and correspond to influenza and seasonal respiratory infections in temperate and tropical climates. We believe the effect of supersaturation in the airways can be the key to understanding of ‘the age-old epidemiologic mystery of influenza seasonality in the different climatic conditions’.

We have originally shown for the first time the two different climatic patterns of seasonality of influenza and common colds have an only one common “link”. It is the effect of supersaturation and condensational growth in the upper airways which occurs under specific environmental conditions when flu seasons take place in the tropical/subtropical and temperate regions. We have found that under climatic conditions which are peculiar to the seasonal patterns of influenza and common colds (“humid-rainy” and “cold-dry”) the effect of supersaturation and condensational growth may be additional factor/reason leading to the next: - dramatic rise of deposition rate of infectious agents from inhaled air in the upper airways; - additional acidification of epithelial lining fluid in the local areas of the respiratory tract, and, as a result, may lead to destructive impacts on host cells and weakening of the defense mechanisms of the airways; - additional affecting on the critical local cooling and reducing (as a consequence) the antiviral immune response of the airway epithelial cells. Thus, the effect of supersaturation and condensational growth can act as a common trigger for influenza, common colds and other respiratory infection in both mid-latitudes and in the tropics/subtropics.

Objective: In this study the main aspects of influenza transmission via fine and ultrafine bioaerosols were considered. Here, we aimed to estimate the impact of the different environment conditions on the deposition rate of the infectious bioaerosols in the respiratory tract. Background: The latest researches show the infected people generate the fine and ultrafine infectious bioaerosols with submicron particles/droplets (size below 1 µm). The airborne transmission of these particles/droplets in the environment is effective. It is considered the deposition of submicron particles in the respiratory tract (RT) has very low probability. But most studies examined the aerosol deposition in RT under normal environmental conditions and did not paid attention to the affecting the different environmental factors. Methods: We review the problems of epidemiology of respiratory infections and aspects of airborne transmission/spread of infectious agents. We contrast these approaches with known data from next areas: inhalation toxicology, respiratory drug delivery and physics of heat and mass transfer in the airways. Results: Based on the conducted analysis, we propose the next main concepts: 1 Breathing cool air leads to the supersaturation of air in RT; 2 the air supersaturation leads to the intensive condensational growth(CG) of inhaled viruses or bacteria in RT; 3 CG leads to the intensive and dramatically growth of deposition rate of viruses or bacteria in RT. We have shown: a) Under normal conditions of inhaled air (T>20˚C; Relatively Humidity, RH=60%) there is no transition in supersaturated condition in RT and CG is insignificant and probability of virus deposition on epithelium of RT is low – no more than 20%. b) Breathing cool/cold air of T<+15˚C and RH of [30..60]% leads to the supersaturation in the airways and it can dramatically increase the deposition rate of inhaled bioaerosols in RT(up to 96%). c) With an increase in RH of inhaled air the supersaturation in RT occurs even at warm temperature of inhaled air (for inhaled air of T<20°C and RH>70% ; T<25°C and RH>90%). Which also indicates the deposition rate of bioaerosols in RT under these conditions is high. Conclusion: Under specific environmental conditions (when flu seasons) the processes of supersaturation in the RT can be observed. These results indicate the high probability of virus deposition on epithelium of RT and correspond to influenza and seasonal respiratory infections in temperate and tropical climates. We believe the effect of supersaturation in the airways can be the key to understanding of ‘the age-old epidemiologic mystery of influenza seasonality in the different climatic conditions’.

There are many theories of the seasonality of influenza for different climatic zones. But none of the known theories provides a clear explanation, especially for the tropical and subtropical climate. Here we have originally analyzed the association/connection of activity of seasonal influenza in Okinawa (subtropical zone) with the probability of occurring of supersaturation in the human airways when inhaling environmental air under specific weather conditions. We have shown for the first time that the effects of supersaturation in the human airways may be associated with main representative peaks of intensity/activity of influenza in Okinawa in the period of observation from Jan 2007 until Dec 2012 including 2009 pandemic. Our observation is the first one which clearly shows in the practice that the effect of supersaturation in the airways can be used for understanding and forecast the influenza activity in subtropical and tropical zones. Because the effect of supersaturation may lead to an additional risk of acidification of epithelial lining fluid in the local areas of the respiratory tract and to additional risk of deposition of infectious agents from inhaled air in the upper airways.

10We have originally shown for the first time the two different climatic patterns of 11 seasonality of influenza and common colds have an only one common "link". It is the 12 effect of supersaturation and condensational growth in the upper airways which occurs 13 under specific environmental conditions when flu seasons take place in the 14 tropical/subtropical and temperate regions. 15 We have found that under climatic conditions which are peculiar to the seasonal 16 patterns of influenza and common colds ("humid-rainy" and "cold-dry") the effect of 17 supersaturation and condensational growth may be additional factor/reason leading to the