The Respiratory System

The respiratory system is a vital biological system responsible for the  exchange of gases between the body and the environment. It consists of  the upper respiratory tract (including the nose, nasal cavity, pharynx,  and larynx) and the lower respiratory tract (including the trachea,  bronchi, bronchioles, and lungs). The primary function of the  respiratory system is respiration, which involves the intake of oxygen  from the air and the expulsion of carbon dioxide produced by cellular  metabolism. During inhalation, air enters the respiratory system through  the nose or mouth, travels down the airways, and reaches the lungs,  where oxygen diffuses into the bloodstream while carbon dioxide is  expelled during exhalation. Additionally, the respiratory system plays a  role in other physiological processes, such as vocalization, odor  detection, and the regulation of pH balance and blood pressure through  the control of carbon dioxide levels. 

 Chronic Obstructive Pulmonary Disease (COPD): A group of progressive lung diseases, including emphysema and chronic bronchitis, characterized by airflow limitation, difficulty breathing, coughing, and excessive mucus production.

• Asthma: A chronic inflammatory condition of the airways, causing episodes of wheezing, chest tightness, shortness of breath, and coughing, triggered by various factors such as allergens, exercise, or respiratory infections.
• Pneumonia: Inflammation of the lung tissue, typically caused by bacterial, viral, or fungal infections, leading to symptoms such as fever, cough, chest pain, and difficulty breathing.
• Lung Cancer: A malignant tumor arising from the cells of the lung tissue, often associated with smoking or exposure to carcinogens, leading to symptoms such as persistent cough, chest pain, weight loss, and difficulty breathing.
• Obstructive Sleep Apnea (OSA): A sleep disorder characterized by repetitive episodes of complete or partial upper airway obstruction during sleep, leading to disrupted breathing, snoring, daytime sleepiness, and increased risk of cardiovascular disease.
• Pulmonary Embolism (PE): A blockage of the pulmonary artery or its branches by a blood clot, fat, air bubble, or other substances, leading to symptoms such as sudden chest pain, shortness of breath, rapid heart rate, and coughing up blood.

 Hyperinsulinemia, insulin resistance, and metabolic syndrome may contribute to the development or exacerbation of respiratory system disorders through various mechanisms:

• Inflammation: Insulin resistance and metabolic abnormalities are associated with chronic low-grade inflammation, which may contribute to airway inflammation and respiratory symptoms in conditions such as COPD, asthma, and pneumonia.
• Oxidative Stress: Metabolic abnormalities can lead to increased oxidative stress, which may damage lung tissue and exacerbate respiratory diseases like COPD and asthma.
• Obesity: Metabolic syndrome components such as obesity are significant risk factors for respiratory disorders like obstructive sleep apnea and obesity-related hypoventilation syndrome, leading to airway obstruction, hypoventilation, and impaired gas exchange during sleep.
• Immune Dysfunction: Insulin resistance and metabolic disturbances can impair immune function, potentially increasing susceptibility to respiratory infections such as pneumonia and exacerbating inflammatory responses in chronic respiratory conditions.
• Thrombosis: Hyperinsulinemia and metabolic abnormalities may increase the risk of thrombotic events such as pulmonary embolism, which can lead to acute respiratory symptoms and potentially life-threatening complications.

Overall, while the direct influence of metabolic abnormalities on the respiratory system disorders may vary, their effects on inflammation, oxidative stress, obesity, immune function, and thrombosis may indirectly contribute to the development or exacerbation of respiratory diseases.

 Diabetes-related complications such as cardiovascular disease and  neuropathy can affect respiratory function. Additionally, diabetes  increases the risk of respiratory infections and exacerbates  pre-existing respiratory conditions due to compromised immune function  and impaired lung tissue repair mechanisms. 

" MetS was associated with worse lung function according to all the spirometric parameters analyzed ...  The findings have shown that an increase in cardiometabolic risk factors  is associated with a more significant worsening of spirometric  variables and a higher prevalence of Restrctive Lund Disease  RLD and MLD. (Mixed Lung Disease) As spirometry could be  a crucial tool for monitoring patients at risk of developing chronic  pathologies, we conclude that this inexpensive and easily accessible  test could help detect changes in lung function in patients with  cardiometabolic disorders. This highlights the need to consider the  importance of cardiometabolic health in lung function when formulating  public health policies.      

 Excess adipose tissue can lead to mechanical compression of the chest  cavity, reducing lung volumes and impairing diaphragmatic function.  Obesity is also strongly associated with conditions such as obstructive  sleep apnea (OSA) and obesity hypoventilation syndrome (OHS), which can  result in respiratory difficulties, daytime fatigue, and impaired gas  exchange. 

" Obesity causes mechanical compression of the diaphragm, lungs, and chest  cavity, which can lead to restrictive pulmonary damage. Furthermore,  excess fat decreases total respiratory system compliance, increases  pulmonary resistance, and reduces respiratory muscle strength. It is  interesting that metabolic syndrome also changes lung function and that  the combination of obesity and metabolic syndrome seems to impair lung  function even further. In obese and overweight patients, a strong  correlation exists between lung function and body fat distribution, with  greater impairment when fat accumulates in the chest and abdomen.  Despite advances in the knowledge of pulmonary and systemic  complications and of the biochemical abnormalities associated with  obesity, longitudinal randomized studies are needed to assess the impact  of weight loss on metabolic syndrome and lung function. "

 Diabetes-related complications such as cardiovascular disease and  neuropathy can affect respiratory function. Additionally, diabetes  increases the risk of respiratory infections and exacerbates  pre-existing respiratory conditions due to compromised immune function  and impaired lung tissue repair mechanisms. 

1. Alessandro  R, Gerardo B, Alessandra L, et al. Effects of Twenty Days of the  Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy  Subjects. Lung. 2015;193(6):939-945. doi:10.1007/s00408-015-9806-7 ABSTRACT
2. Suteerojntrakool  O, Sanguanrungsirikul S, Sritippayawan S, Jantarabenjakul W,  Sirimongkol P, Chomtho S. Effect of a low-carbohydrate diet on  respiratory quotient of infants with chronic lung disease. J Med Assoc  Thai. 2015;98 Suppl 1:S21-28. PMID: 25764609 ABSTRACT
3. Stubbs  BJ, Koutnik AP, Goldberg EL, et al. Investigating Ketone Bodies as  Immunometabolic Countermeasures against Respiratory Viral Infections.  Med (N Y). Published online July 15, 2020. doi:10.1016/j.medj.2020.06.008 
4. Gorji  Z, Modaresi M, Yekanni-Nejad S, Rezaei N, Mahmoudi M. Comparing effects  of low glycemic index/high-fat, high-calorie diet and high-fat,  high-calorie diet on cytokine levels of patients with cystic fibrosis: A  randomized controlled clinical trial. Eur Cytokine Netw. 2020;31(1):32-38. doi:10.1684/ecn.2020.0442
5. Chen W-L, Wang C-C, Wu L-W, et al. Relationship between Lung Function and Metabolic Syndrome. PLOS ONE. 2014;9(10):e108989. doi:10.1371/journal.pone.0108989
6. de  Boer GM, Tramper-Stranders GA, Houweling L, et al. Adult but not  childhood onset asthma is associated with the metabolic syndrome,  independent from body mass index. Respiratory Medicine. 2021;188:106603. doi:10.1016/j.rmed.2021.106603
7. Kim  S H, Min H K, Kim H S, Lee S W. Association between insulin resistance  and lung function change: Analysis from the community-based prospective  Ansan-Ansung cohort in Korea. Published online November 4, 2020. doi:10.21203/rs.3.rs-101239/v1 
8. Kim  SH, Kim HS, Min HK, Lee SW. Association between insulin resistance and  lung function trajectory over 4 years in South Korea: community-based  prospective cohort. BMC Pulmonary Medicine. 2021;21(1):110. doi:10.1186/s12890-021-01478-7
9. Lee  S-A, Joshi P, Kim Y, Kang D, Kim WJ. The Association of Dietary  Macronutrients with Lung Function in Healthy Adults Using the  Ansan-Ansung Cohort Study. Nutrients. 2020;12(9):2688. doi:10.3390/nu12092688
10. al-Saady  NM, Blackmore CM, Bennett ED. High fat, low carbohydrate, enteral  feeding lowers PaCO2 and reduces the period of ventilation in  artificially ventilated patients. Intensive Care Med. 1989;15(5):290-295. doi:10.1007/bf00263863 ABSTRACT
11. Gangitano, E. et al. (2021) ‘Ketogenic Diet for Obese COVID-19 Patients: Is Respiratory  Disease a Contraindication? A Narrative Review of the Literature on  Ketogenic Diet and Respiratory Function’, Frontiers in Nutrition, 8. doi:10.3389/fnut.2021.771047.
12. Gangitano E, Tozzi R, Gandini O, et al. Ketogenic Diet as a Preventive and Supportive Care for COVID-19 Patients. Nutrients. 2021;13(3):1004. doi:10.3390/nu13031004
13. Goldberg  EL, Molony RD, Kudo E, et al. Ketogenic diet activates protective γδ T  cell responses against influenza virus infection. Sci Immunol.  2019;4(41). doi:10.1126/sciimmunol.aav2026  (Pre-Clinical)

Asthma is a chronic inflammatory condition of the airways, causing episodes of wheezing, chest tightness, shortness of breath, and coughing. 

While asthma is primarily considered an inflammatory disorder, there is growing evidence suggesting a potential link between insulin resistance and asthma development or exacerbations. Insulin resistance may contribute to airway inflammation and hyperresponsiveness, which are hallmark features of asthma. Moreover, obesity, a common feature of metabolic syndrome, is a significant risk factor for asthma and can exacerbate symptoms by promoting airway inflammation and mechanical changes in lung function.

There is mounting evidence that linoleic acid and its metabolites affect paediatric asthma. Further investigation is need on the tioming and mechanism of this exposure to determine if dietary interventions could help prevent paediatric asthma 

" Obesity, insulin resistance or glucose intolerance, dyslipidemia, and  other key clinical features of metabolic dysfunction—typically  manifested as metabolic syndrome—have been found to be possible risk  factors for severe and uncontrolled asthma. More specifically, disorders  of glucose metabolism, ranging from clinically silent insulin  resistance through degrees of hyperglycemia defining prediabetes and  diabetes, can precipitate changes in the lung consistent with asthma  through pathways principally involving insulin excess. Recent  experimental studies have shown that insulin resistance may contribute  to an increase in systemic inflammation, modulation of immune function,  effects on airway remodeling, promotion of airway smooth muscle (ASM)  contractility and proliferation and increase of airway  hyper-responsiveness. Evidence from observational studies also supports  clinically relevant associations between glycemic dysregulation and  asthma outcomes. In our opinion, there are four mechanisms of the effect  of insulin resistance in asthma: (i) aging is associated with insulin  resistance, which can lead to premature airway closure and airway  damage, (ii) insulin directly contributes to airway dysfunction by  causing airway inflammation through the activation of immunological and  structural cells in the lungs, (iii) insulin can directly induce airway  hyperresponsiveness by promoting the deposition of collagen fibroblasts  in the airways, (iv) insulin is a pleiotropic hormone that affects  endothelial cells in a variety of ways. "

Background: Airflow obstruction in asthma is usually reversible, but fixed obstruction develops in some individuals. Little is known about risk factors for development of fixed airflow obstruction in nonsmokers with asthma. 

Methods: This case-comparison study recruited nonsmokers aged over 45 years with physician-diagnosed asthma from specialist outpatient clinics and primary care. Two age-matched groups were recruited on the basis of spirometry: anobstructed group (post-bronchodilator FEV(1) ≤ 70% predicted, FEV1/FVC ratio < lower limit of normal) and a control group with normal lung function. Subjects completed a questionnaire and interview, and underwent spirometry, venesection, exhaled nitric oxide (ENO) measurement, allergen skinprick testing, and formal lung function testing. 

Results: Thirty-four obstructed subjects and 40 controls participated in the study. Obstructed subjects exhibited greater evidence of systemic inflammation, abnormal glucose homeostasis, and central obesity than controls. Obstructed subjects reported longer duration of asthma, and childhood respiratory infection was commoner in that group. Metabolic syndrome prevalence was similar between groups, but several features of insulin resistance were associated with reduced FEV(1). Cough and sputum were common among controls. 

Conclusions: Risk of fixed airflow obstruction may correlate with lifetime asthma duration. Individuals with coexisting asthma and fixed airflow obstruction have heightened systemic inflammation. A variety of chronic respiratory symptoms are common among "healthy" nonsmokers with asthma. 

1. Alsharairi, N.A.  (2020) ‘The Role of Short-Chain Fatty Acids in the Interplay between a  Very Low-Calorie Ketogenic Diet and the Infant Gut Microbiota and Its  Therapeutic Implications for Reducing Asthma’, International Journal of Molecular Sciences, 21(24), p. 9580. Available at: https://doi.org/10.3390/ijms21249580.
2. Al-Rebdi, M. and Rabbani, U. (2023) ‘Alleviation of Asthma Symptoms After Ketogenic Diet: A Case Report’, Cureus [Preprint]. Available at: https://doi.org/10.7759/cureus.34526.
3. Yang  G, Han Y-Y, Forno E, et al. Glycated hemoglobin A1c, lung function, and  hospitalizations among adults with asthma. J Allergy Clin Immunol  Pract. Published online June 19, 2020. doi:10.1016/j.jaip.2020.06.017 ABSTRACT
4. Nejatifar  F, Foumani AA, Poor ARG, Nejad AT .Association of Metabolic Syndrome  and Asthma Status; A Prospective Study from Guilan Province-Iran. –  Abstract – Europe PMC. doi:10.2174/1871530321666210305125059 
5. Wu  TD. Diabetes, insulin resistance, and asthma: a review of potential  links. Current Opinion in Pulmonary Medicine. Published online September  29, 2020. doi:10.1097/MCP.0000000000000738
6. Al-Sharif  FM, Abd El-Kader SM, Neamatallah ZA, AlKhateeb AM. Weight reduction  improves immune system and inflammatory cytokines in obese asthmatic  patients. Afr Health Sci. 2020;20(2):897-902. doi:10.4314/ahs.v20i2.44 
7. Alsharairi  NA. The Role of Short-Chain Fatty Acids in the Interplay between a Very  Low-Calorie Ketogenic Diet and the Infant Gut Microbiota and Its  Therapeutic Implications for Reducing Asthma. International Journal of Molecular Sciences. 2020;21(24):9580. doi:10.3390/ijms21249580 
8. de  Boer GM, Tramper-Stranders GA, Houweling L, et al. Adult but not  childhood onset asthma is associated with the metabolic syndrome,  independent from body mass index. Respiratory Medicine. 2021;188:106603. doi:10.1016/j.rmed.2021.106603 
9. Ghatas, T.S. (2021) ‘Metabolic syndrome and asthma’, Journal of Medicine in Scientific Research, 4(4), p. 314. doi:10.4103/jmisr.jmisr_34_21.
10. Goyal JP, Kumar P, Thakur C, Khera D, Singh K, Sharma P. Effect of insulin resistance on lung function in asthmatic children. J Pediatr Endocrinol Metab. Published online October 1, 2021. doi:10.1515/jpem-2021-0351 ABSTRACT
11. Carr  TF, Granell R, Stern DA, et al. High Insulin in Early Childhood is  Associated with Subsequent Asthma Risk Independent of Body Mass Index. The Journal of Allergy and Clinical Immunology: In Practice. Published online October 14, 2021. doi:10.1016/j.jaip.2021.09.047 ABSTRACT
12. Buendia  J, Acuña-Cordero R, TALAMONI H. The role of high carbohydrate-rich food  intake and severity of wheezing exacerbation in children between 2 to 6  years aged. Published online 2021. doi:10.22541/au.162536704.41003159/v1 ABSTRACT
13. Calcaterra  V, Verduci E, Ghezzi M, et al. Pediatric Obesity-Related Asthma: The  Role of Nutrition and Nutrients in Prevention and Treatment. Nutrients. 2021;13(11):3708. doi:10.3390/nu13113708

COPD is a progressive lung disease characterized by airflow limitation that makes it difficult to breathe. It typically includes two main conditions: emphysema and chronic bronchitis. Common symptoms include shortness of breath, coughing, wheezing, and chest tightness. Emphysema involves damage to the air sacs in the lungs, leading to decreased lung elasticity and difficulty exhaling air. Chronic bronchitis involves inflammation and narrowing of the airways, resulting in excessive mucus production and persistent cough.

Hyperinsulinemia: Elevated insulin levels may contribute to systemic inflammation, which can exacerbate airway inflammation and lung damage in individuals with COPD.

Insulin Resistance: Insulin resistance has been associated with impaired lung function and increased risk of COPD exacerbations. It may also contribute to oxidative stress and inflammation in the lungs.

Metabolic Syndrome: Components of metabolic syndrome such as obesity and dyslipidemia can worsen COPD outcomes by increasing the risk of respiratory infections, exacerbations, and mortality. Obesity is particularly associated with decreased lung function and exercise capacity in individuals with COPD

1. Tümer  G, Mercanligi̇l SM, Uzun O, Aygün C. The Effects of a High-Fat,  Low-Carbohydrate Diet on the Prognosis of Patients with an Acute Attack  of Chronic Obstructive Pulmonary Disease. Turkiye Klinikleri J Med Sci. 2009;29(4):895-904. ISSN:1300-0292 ABSTRACT
2. Adherence  to Low Carbohydrate Diet in Relation to Chronic Obstructive Pulmonary  Disease (COPD). Published online December 11, 2020. (Research Square –  Pre-print) doi:10.21203/rs.3.rs-125271/v1
3. Cai B, Zhu Y, Ma Y i, et al. Effect of Supplementing a High-Fat, Low-Carbohydrate Enteral Formula in COPD Patients. Nutrition (Burbank, Los Angeles County, Calif). 2003;19:229-232. doi:10.1016/S0899-9007(02)01064-X ABSTRACT
4. Angelillo  VA, Bedi S, Durfee D, Dahl J, Patterson AJ, O’Donohue WJ. Effects of  low and high carbohydrate feedings in ambulatory patients with chronic  obstructive pulmonary disease and chronic hypercapnia. Ann Intern Med. 1985;103(6 ( Pt 1)):883-885. doi:10.7326/0003-4819-103-6-883 ABSTRACT
5. Norwitz  NG, Winwood R, Stubbs BJ, D’Agostino DP, Barnes PJ. Case Report:  Ketogenic Diet Is Associated With Improvements in Chronic Obstructive  Pulmonary Disease. Front Med. 2021;0. doi:10.3389/fmed.2021.699427
6. Katsiki  N, Stoian AP, Steiropoulos P, Papanas N, Suceveanu AI, Mikhailidis DP.  Metabolic Syndrome and Abnormal Peri-Organ or Intra-Organ Fat (APIFat)  Deposition in Chronic Obstructive Pulmonary Disease: An Overview. Metabolites. 2020;10(11):465. doi:10.3390/metabo10110465
7. Scoditti E, Massaro M, Garbarino S, Toraldo DM. Role of Diet in Chronic Obstructive Pulmonary Disease Prevention and Treatment. Nutrients. 2019;11(6). doi:10.3390/nu11061357

 CFRD is a common complication of cystic fibrosis (CF), a genetic disorder that primarily affects the lungs and digestive system. CFRD is characterized by abnormal glucose metabolism and insulin secretion due to pancreatic damage and fibrosis. It shares features with both type 1 and type 2 diabetes, often presenting with impaired glucose tolerance or frank diabetes. Symptoms may include increased thirst, frequent urination, weight loss, and fatigue.

 While CFRD is primarily driven by pancreatic dysfunction in cystic fibrosis, the presence of hyperinsulinemia, insulin resistance, and metabolic syndrome can further complicate glucose metabolism in affected individuals. Insulin resistance, commonly observed in CF patients, may exacerbate glycemic control difficulties and increase the risk of CFRD development or progression. Additionally, metabolic syndrome-related factors such as obesity and dyslipidemia may contribute to insulin resistance and worsen glycemic control in CFRD patients, potentially leading to more severe complications.

 Lung cancer is a malignant tumor arising from lung tissue cells, commonly associated with smoking or exposure to carcinogens. While the direct influence of hyperinsulinemia, insulin resistance, or metabolic syndrome on lung cancer development is not fully elucidated, insulin resistance and hyperinsulinemia have been implicated in promoting cancer cell growth and metastasis through various pathways, including insulin-like growth factor (IGF) signaling and inflammation. Additionally, metabolic syndrome components like obesity are independent risk factors for lung cancer and may contribute to its pathogenesis. 

  Smoking tobacco is the major risk factor for developing lung cancer.  However, most Han Chinese women with lung cancer are nonsmokers. Chinese  cooking methods usually generate various carcinogens in fumes that may  inevitably be inhaled by those who cook the food, most of whom are  female. We investigated the associations of cooking habits and exposure  to cooking fumes with lung cancer among non-smoking Han Chinese women.  This study was conducted on 1,302 lung cancer cases and 1,302 matched  healthy controls in Taiwan during 2002–2010. Two indices, “cooking  time-years” and “fume extractor use ratio,” were developed. The former  was used to explore the relationship between cumulative exposure to  cooking oil fumes and lung cancer; the latter was used to assess the  impact of fume extractor use for different ratio-of-use groups. Using  logistic models, we found a dose–response association between cooking  fume exposure and lung cancer (odds ratios of 1, 1.63, 1.67, 2.14, and  3.17 across increasing levels of cooking time-years). However, long-term  use of a fume extractor in cooking can reduce the risk of lung cancer  by about 50%. Furthermore, we provide evidence that cooking habits,  involving cooking methods and oil use, are associated with risk of lung  cancer. 

 Mitochondria are pivotal for respiratory health, driving cellular  respiration to power essential processes in the respiratory system. They  provide the energy necessary for respiratory muscle contraction,  enabling efficient breathing and oxygen uptake. Dysfunctional  mitochondria within respiratory cells can lead to impaired energy  production, contributing to respiratory conditions like chronic  obstructive pulmonary disease (COPD) and asthma. Moreover, mitochondria  regulate immune responses in the respiratory system, essential for  defending against infections. Nutrient-dense whole foods support optimal  mitochondrial function, while processed foods lacking essential  nutrients may contribute to oxidative stress and inflammation,  compromising respiratory health. Prioritizing a diet rich in whole foods  is vital for preserving mitochondrial health and reducing the risk of  respiratory diseases, underscoring the importance of dietary choices in  maintaining respiratory function and well-being. 

"! Accumulating evidence demonstrates that mitochondrial dysfunction can  act as a key mediator of the pathogenesis of many diseases, including  human chronic parenchymal lung diseases. Mitochondrial autophagy  (mitophagy), activated in response to mitochondrial injury incurred by  noxious stimuli, plays a complex role in the lung, where it can have  both protective and injurious effects on the progression of lung  disease. "

" Mitochondria are now thought of as one of the cell’s most sophisticated  and dynamic responsive sensing systems. Specific signatures of  mitochondrial dysfunction that are associated with disease pathogenesis  and/or progression are becoming increasingly important. In particular,  the centrality of mitochondria in the pathological processes and  clinical phenotypes associated with a range of lung diseases is  emerging. "

" Chronic obstructive pulmonary disease (COPD) is a devastating lung  disease for which cigarette smoking is the main risk factor.  Acetaldehyde, acrolein, and formaldehyde are short-chain aldehydes known  to be formed during pyrolysis and combustion of tobacco and have been  linked to respiratory toxicity. Mitochondrial dysfunction is suggested  to be mechanistically and causally involved in the pathogenesis of  smoking-associated lung diseases such as COPD. Cigarette smoke (CS) has  been shown to impair the molecular regulation of mitochondrial  metabolism and content in epithelial cells of the airways and lungs.  Although it is unknown which specific chemicals present in CS are  responsible for this, it has been suggested that aldehydes may be  involved. Therefore, it has been proposed by the World Health  Organization to regulate aldehydes in commercially-available cigarettes.  In this review, we comprehensively describe and discuss the impact of  acetaldehyde, acrolein, and formaldehyde on mitochondrial function and  content and the molecular pathways controlling this (biogenesis versus  mitophagy) in epithelial cells of the airways and lungs. In addition,  potential therapeutic applications targeting (aldehyde-induced)  mitochondrial dysfunction, as well as regulatory implications, and the  necessary required future studies to provide scientific support for this  regulation, have been covered in this review. 

" Chronic obstructive pulmonary disease (COPD) is a devastating lung  disease for which cigarette smoking is the main risk factor.  Acetaldehyde, acrolein, and formaldehyde are short-chain aldehydes known  to be formed during pyrolysis and combustion of tobacco and have been  linked to respiratory toxicity. Mitochondrial dysfunction is suggested  to be mechanistically and causally involved in the pathogenesis of  smoking-associated lung diseases such as COPD. Cigarette smoke (CS) has  been shown to impair the molecular regulation of mitochondrial  metabolism and content in epithelial cells of the airways and lungs.  Although it is unknown which specific chemicals present in CS are  responsible for this, it has been suggested that aldehydes may be  involved. Therefore, it has been proposed by the World Health  Organization to regulate aldehydes in commercially-available cigarettes.  In this review, we comprehensively describe and discuss the impact of  acetaldehyde, acrolein, and formaldehyde on mitochondrial function and  content and the molecular pathways controlling this (biogenesis versus  mitophagy) in epithelial cells of the airways and lungs. In addition,  potential therapeutic applications targeting (aldehyde-induced)  mitochondrial dysfunction, as well as regulatory implications, and the  necessary required future studies to provide scientific support for this  regulation, have been covered in this review. 

 Fats are also a significant source of aldehydes, and when cooked, over 20 different aldehydes are produced [66],  Aldehydes are formed when frying food or heating oils to cook food.  These aldehydes are mainly generated from the thermal oxidation of the  polyunsaturated triacylglycerols [67].  Cooking oil heated at a temperature of 180 °C produces high amounts of  aerosolized acrolein (canola oil 53.5 ± 3.9 mg/h and safflower oil 57.3 ±  6.7 mg/h) which are typically inhaled while standing over cooking food [68].  When soybean oil is used to cook deep-fried potatoes, 4-hydroxynonenal  (4-HNE) is a major polar lipophilic compound in the thermally oxidized  frying oil [69],  Additional studies further validate that deep-frying food, especially  at high temperatures and for prolonged periods of time, generate  reactive aldehydes [70, 71].  For example, in Taiwan restaurant exhaust streams, 18 carbonyl species  were measured. Formaldehyde, acetaldehyde, acetone, and butyraldehyde  contributed 55.01–94.52% of total carbonyls in the dining areas for the  restaurants measured [72]. 

 At the forefront of protection from environmental sources of reactive  aldehydes is public awareness. Unless knowledge is properly  disseminated, individuals will not be cognizant of the risks associated  with reactive aldehyde exposure or capable of taking the necessary steps  to minimize exposure. Precautionary measures and lifestyle  modifications to reduce reactive aldehyde exposure should be a focus of  public health to ultimately reduce the potential risk for developing  cancer or cardiovascular disease. 

 A venous thromboembolism (VTE) is a condition characterized by the formation of blood clots (thrombi) within the veins, typically in the deep veins of the legs (deep vein thrombosis, DVT), although they can occur in other parts of the body as well. These blood clots can break loose and travel through the bloodstream to other parts of the body, causing blockages in blood vessels, known as embolisms. When a clot travels to the lungs and blocks blood flow, it is called a pulmonary embolism (PE), which can be life-threatening.

Risk factors for developing a VTE include prolonged immobility (such as during long periods of travel or bed rest), surgery, injury, certain medical conditions like cancer and heart disease, hormonal factors (such as pregnancy or estrogen therapy), and genetic predispositions that affect blood clotting.

Symptoms of a VTE may include swelling, pain, tenderness, warmth, and redness in the affected limb in the case of DVT. Symptoms of a pulmonary embolism may include sudden onset of shortness of breath, chest pain, rapid heart rate, and coughing up blood.

Treatment for VTE typically involves anticoagulant medications to prevent further clotting and reduce the risk of complications. In some cases, procedures like thrombolytic therapy or placement of a vena cava filter may be necessary, especially for severe or recurrent cases. Prevention strategies include early mobilization after surgery, use of compression stockings, and anticoagulant medications in high-risk situations.

 Hyperinsulinemia, insulin resistance, and metabolic syndrome can all contribute to the development of venous thromboembolism (VTE) through various mechanisms:

Prothrombotic State: Insulin resistance, which is a hallmark of metabolic syndrome, can lead to alterations in the body's clotting mechanisms, favoring a prothrombotic state. Insulin resistance is associated with increased levels of clotting factors and decreased levels of anticoagulant proteins, promoting blood clot formation.

Endothelial Dysfunction: Hyperinsulinemia and insulin resistance can cause endothelial dysfunction, impairing the function of the inner lining of blood vessels. Endothelial dysfunction is associated with increased inflammation and reduced production of vasodilators, which can contribute to a hypercoagulable state and predispose individuals to thrombosis.

Obesity: Metabolic syndrome often includes obesity as a component, and obesity is an independent risk factor for VTE. Adipose tissue produces inflammatory cytokines and other factors that can promote clot formation and impair fibrinolysis, the process of breaking down blood clots.

Dyslipidemia: Metabolic syndrome is characterized by dyslipidemia, including elevated triglycerides and decreased high-density lipoprotein (HDL) cholesterol levels. Dyslipidemia can contribute to endothelial dysfunction and inflammation, further increasing the risk of VTE.

Hyperglycemia: Elevated blood glucose levels, which are common in hyperinsulinemia and insulin resistance, can promote oxidative stress and inflammation, damaging blood vessels and promoting thrombosis.

Venous Stasis: Insulin resistance and obesity are associated with conditions such as immobility and venous stasis, which can impair blood flow in the veins and increase the risk of blood clot formation, particularly in the deep veins of the legs.

Hormonal Effects: Insulin and insulin-like growth factor-1 (IGF-1) have been shown to have direct effects on platelet function and coagulation pathways, potentially promoting thrombosis in individuals with hyperinsulinemia and insulin resistance.

Overall, hyperinsulinemia, insulin resistance, and metabolic syndrome can contribute to a prothrombotic state through multiple pathways, including alterations in clotting factors, endothelial dysfunction, inflammation, obesity, dyslipidemia, hyperglycemia, venous stasis, and hormonal effects. These factors increase the risk of developing venous thromboembolism, including deep vein thrombosis and pulmonary embolism.