THE BENEFITS OF SMOKING CESSATION ON PATIENTS WITH COPD – A NARRATIVE REVIEW

103 TB S C PHE ENEFITS OF MOKING ESSATION ON ATIENTS WITH ARRATIVE EVIEWCOPD – A N R Antonio-Andrei Cotea , Andreea Tirnoveanu , Andreea-Nicoleta Malaescu , 1,5 4,5* 1,2,5 Andreea-Roxana Florescu , Marius Eremia , Florin-Dumitru Mih an , 1,3,5 5 1,2,5 ăl Ancu a-Alina Constantin 1,2 Corresponding Author: Andreea Tirnoveanu4,5* 1. National Institute of Pneumophthisiology "Marius Nasta", Bucharest; 2. "Carol Davila" University of Medicine and Pharmacy, Bucharest; 3. “Victor Babeș” University of Medicine and Pharmacy, Timișoara; 4. Grigore T. Popa University of Medicine and Pharmacy, Iași, Romania; 5. AerPur Romania, Bucharest, Romania. Abstract Chronic obstructive pulmonary disease (COPD) is a major healthcare problem and an important cause of mortality worldwide, causing 3,23 million deaths in 2019, 90% of COPD deaths in those under the age of 70 in low and middle-income countries according to WHO (World Health Organization). COPD is the third leading cause of death globally, with 24% of patients dying within five years of diagnosis . Smoking is the most common risk factor for COPD, as tobacco [1] smoke contains a large number of toxic substances that are both the cause of COPD and the main factor implicated in the progression of the disease . [2] This narrative review aims to provide scientific help to healthcare professionals to understand the importance of focusing on smoking cessation amongst patients with COPD as the main treatment method, besides pharmacological therapy. The global burden of COPD mortality must be addressed through efforts to reduce exposure to risk factors, assess individual patient risk, and use treatments that lower mortality. In countries that have adopted comprehensive strategies for prevention and treatment, COPD-related mortality rates have declined. The latest research points out the importance of smoking cessation in the prognosis and quality of life among COPD patients. Keywords: Tobacco smoking, chronic obstructive pulmonary disease, COPD, smoking cessation. Rezumat Boala pulmonară obstructivă cronică (BPOC) este o problemă majoră de asistenă medicală și o cauză importantă de mortalitate la nivel mondial, provocând 3,23 milioane de decese în 2019, 90% din decesele BPOC la cei sub 70 de ani în ările cu venituri mici și medii, conform OMS (Organizaia Mondială a Sănătăii). BPOC este a treia cauză de deces la nivel global, 24% dintre General Reviews Internal Medicine 20 4 vol. X I No. 4 - www.srmi.ro2X /inmed-20 4-031210.2478 2 104 Introduction COPD is a chronic, incurable, and lifethreatening respiratory disease caused by various factors. It is a major cause of morbidity and mortality in economically developed nations and is increasingly emerging as a significant health concern in developing countries . COPD is [3] characterized by chronic airflow limitation, that is not entirely reversible, generally progressive, and associated with an inflammatory pulmonary response to toxic particles and gases . [4] COPD is a widespread disease, affecting 10% of the global population, and according to the evaluations performed by WHO, COPD will become the third leading cause of death by 2030 . [5] There are many risk factors for developing COPD, and current research show that smoking, biofuels, indoor, outdoor air pollution and industrial dust are the major environmental risk factors. However, the most important cause of COPD remains cigarette smoking . [3] The 2023 WHO report on the global tobacco epidemic showed that tobacco consumption killed an astounding 8.7 million people every year. And even more shocking is that 1.3 million of these deaths are among people who do not use tobacco, including infants and children. In particular, women and children pacieni decedând în decurs de cinci ani de la diagnosticare. Fumatul este cel mai frecvent factor de risc pentru BPOC, deoarece fumul de tutun conine un număr mare de substane toxice care sunt atât cauza BPOC, cât și principalul factor implicat în progresia bolii. Această revizuire narativă își propune să ofere ajutor știinific profesioniștilor din domeniul sănătăii pentru a înelege importana concentrării asupra renunării la fumat în rândul pacienilor cu BPOC ca metodă principală de tratament, pe lângă terapia farmacologică. Povara globală a mortalităii BPOC trebuie abordată prin eforturi de reducere a expunerii la factorii de risc, evaluarea riscului individual al pacientului și utilizarea tratamentelor care scad mortalitatea. În ările care au adoptat strategii cuprinzătoare de prevenire și tratament, ratele mortalităii legate de BPOC au scăzut. Cele mai recente cercetări subliniază importana renunării la fumat în prognosticul și calitatea vieii în rândul pacienilor cu BPOC. Cuvinte cheie: fumatul de tutun, boală pulmonară obstructivă cronică, BPOC, renunarea la fumat. General Reviews 105 are vulnerable to second-hand smoke exposure . [6] Although passive smoking is also related to developing COPD , active smoking has been [3] associated with COPD severity, patient's quality of life and comorbidities . Cigarette [4] smokers have a higher prevalence of respiratory symptoms, abnormal lung function, a greater annual decline in FEV1 (forced expiratory volume in 1 s) and a great mortality rate compared with non-smokers . [7] In spite of the fact that rate of cigarette smoking is decreasing in several countries, it remains a serious threat to public health worldwide, particularly in South-East Asia as well as in Eastern Europe with the world`s largest number of smokers. The WHO estimates that by 2050 there will be 1,5 billion smokers globally . [8] Even though smoking is the primary cause of COPD, it does not lead to COPD in all smokers, as in the study conducted by Fletcher et al., airway obstruction was observed in 12% of the moderate smokers and 26% of the heavy smokers . [9] Also, in an umbrella review conducted by Holtjer and all. stated that active smoking, as compared to nonsmokers, is the main risk factor for COPD . [10] COPD self-management is an essential component of COPD management behaviors such as quitting smoking, medication adherence, correct inhaler use, healthy diet and physical activity . [11] The importance of smoking cessation cannot be understated, as many studies showed the benefits almost all smokers have regardless the age of quitting or the cumulative amount of tobacco exposure. Whereas the reduction risk is rapid for others diseases such as cardiovascular disease, for cancer and COPD the reduction risk is more gradual, indicating the importance of smoking cessation at a young age in life to maintain respiratory health . [12] Physiopathology COPD is a disease that is characterized by progressive airflow limitation that is not fully reversible and it is associated with an unusual inflammatory response of the lungs to noxious particles and gases . [13] COPD is a complex obstructive illness that includes chronic obstructive bronchiolitis with fibrosis and obstruction of small airways, emphysema with expansion of airspaces and destruction of lung parenchyma, loss of lung elasticity and closure of small airways , but [13] also an increased mucus secretion, plasma leakage and expansion of submucous glands . [9] The primary protective barrier against inhaled toxic substances and microbes is considered to be the bronchial epithelium, as it is playing a vital role in maintaining tissue homeostasis. Any disruption in homeostasis accentuates the inflammatory response and repair process . [14] Irritants in the airways activate various cells that produce and release chemotactic factors that attract additional inflammatory cells . [9] Inhalation of tobacco smoke is a powerful inducer of inflammation both in respiratory tract but also systemically. Tobacco smoke induces mucosal inflammation, heightens oxidative stress and fibrinogen concentration, increases hs-CRP (high-sensitivity C-reactive protein) and expression of inflammatory cytokines . As a result of accumulation of [15] inflammatory mucous exudates in the lumen and an increase in the thickness of the bronchial wall, the inflammatory process persists in those who continue to smoke, despite smoking cessation and progressively worsens over time . Several inflammatory [16] Internal Medicine 20 4 vol. X I No. 4 - www.srmi.ro2X General Reviews 106 cells types are involved in the physiopathology of COPD, including macrophages, neutrophils and T-cells , along [13] with adaptive inflammatory immune cells like CD4, CD8, and B lymphocytes and sometimes eosinophils . [16] Neutrophils are the inflammatory cells that play a central role in the pathogenesis of COPD, sputum and blood neutrophilia is an important hallmark of COPD and a marker of COPD severity . [17] Cigarette smoke reduces the deformability of neutrophil granulocytes which may explain the slow wash out rate of these inflammatory cells from the lungs in smokers . Their [9] accumulation in COPD lungs are significantly increased which is correlated with disease severity and their secreted products have been shown to all major pathological aspects of the condition . Neutrophils release a [18] serine proteases including neutrophil elastases (NE), matrix metalloproteinase (MMP), myeloperoxidase (MPO), all of which have as final result alveolar destruction . [17] Neutrophils from COPD patients have been shown to secrete increased amounts of ROS (reactive oxygen species) both spontaneously and following stimulation . [18] Alveolar macrophages are also key players in airway inflammation in COPD. These cells release a large variety of chemokines and cytokines such as tumor necrosis factor-alpha (TNF-alfa). Alveolar macrophages also produce ROS, MMPs and cathepsins, which contribute to alveolar damage and induce fibrosis mediators such as TGF-beta1 (transforming growth factor-beta-1) to trigger airway remodeling . Macrophage can be [19] directly activated by cigarette smoke and play a key part in sustaining the chronic inflammation in the pulmonary tissue of COPD patients . Alveolar macrophages [16] obtain by bronchoalveolar lavage (BAL) from smokers are primed to release higher amounts of ROS compared with those obtained from non-smokers . [13] In COPD, the adaptive immune system is activated, leading to infiltration of T-cells, Bcells, T-helper type 17 (Th17) cells, along with a reduction in regulatory T cells within the airways. T-lymphocytes numbers are increased in the lung parenchyma and airways of smokers compared with never smokers, regardless of COPD development. CD8 are another cells that increase more significantly than CD4 cells, and this increase in peripheral airways is linked to smokingrelated airway obstruction. The number of Bcells in the lymphoid follicles is also greatly increased in advanced stages of COPD . [17] Another inflammatory cells that are correlated with COPD inflammation are eosinophils, but the role of eosinophils is less certain in COPD than in asthma. Increased numbers of eosinophils have been reported in bronchial biopsies, but also in BAL fluid during General Reviews 107 acute exacerbation of chronic bronchitis . [20] Various inflammatory mediators are implicated in COPD, including lipids, free radicals, cytokines, chemokines and growth factors . [20] Oxidative stress (OS) also plays an important role in COPD giving the increased oxidant burden in smokers . OS has important effects [13] on both lung function and COPD pathogenesis. The most important effects on pathogenesis caused by OS are apoptosis, remodeling of the extracellular matrix, alveolar epithelial injury, mitochondrial respiration, membrane lipid peroxidation (LPO), mucus hypersecretion, and oxidative inactivation of surfactants and antiproteases . [21] In COPD patients, elevated level of OS results from environmental exposure including air pollutants and cigarette smoke, and from the elevated levels of reactive nitrogen species (RNS) and ROS released by macrophages and leukocytes during inflammation . [21] ROS play a critical role in tissue damaging and cell injury linked with numerous inflammatory pulmonary diseases including COPD . Cigarette smoking contains over [21] 1016–1017 oxidants per puff and around 4700 chemicals such as nitrogen oxides, superoxide radicals and peroxynitrite . [21] OS arises from an imbalance between reactive oxygen species production and antioxidant defense. Adequate balance is essential to prevent cellular damage . [22] Increased OS in COPD is linked to impaired antioxidant defenses . [23] Impact of smoking cessation on respiratory symptoms amongst COPD patients As people age, their lung function typically declines, and their ability to repair lung tissue and manage baseline inflammation is reduced. The burden of COPD reaches its peak in older adults, as usually they are patients that have an important variety of comorbid conditions. Combined with the natural increase in comorbidities associated with aging, this results in a higher mortality rate for elderly individuals with COPD . [24] Many studies have examined the impact of smoking on respiratory health. The groundbreaking research by Fletcher and Peto, published in 1977, laid the foundation for our current understanding of how smoking damages lung function and highlighted the critical importance of quitting smoking . [25] The only intervention proven to slow the rate of lung function decline in COPD patients is smoking cessation and is proved that also smoking cessation reduces mortality. From a public health standpoint, smoking cessation is the most effective treatment for COPD and leads to a reduction in symptoms . [26] The Lung Health Study showed that smoking cessation interventions led to a reduction in symptoms such as dyspnea, cough, sputum production, and wheezing. In the study conducted by David H. Au and all. It is shown that individuals who quit smoking earlier in the course of their disease may have milder symptoms and are therefore more likely to experience grater benefits from smoking cessation . [26] Alongside the well-established phenotypes of bronchitis and emphysema, clinicians also identify the phenotype of COPD with frequent exacerbations . Exacerbations in COPD, are [25] known to accelerate the decline in lung function, leading to reduced physical activity, diminished quality of life, and an increased risk of death . [27] There are many factors that lead to COPD exacerbation, but an important role is tobacco smoking. COPD patients who continue to smoke have a high rate of exacerbations that necessitate hospitalization. On the other Internal Medicine 20 4 vol. X I No. 4 - www.srmi.ro2X General Reviews 108 hand, quitting smoking is linked to a lower risk of exacerbations, with the magnitude of risk reduction correlating with the length of time since quitting . [26] COPD exacerbations are characterized by worsening of respiratory symptoms, such as coughing, shortness of breath, increased sputum production and can be triggered by viral or bacterial infection. It is essential to recognize that COPD exacerbations are closely linked to the microbiota in the respiratory tract, microbiota which is disrupted by smoking . [28] There are some studies that discovered that patients with severe COPD have a higher abundance of species from the Lactobacillus genus compared to those with milder or no COPD. Other research has reported increased levels of Veillonella, Streptococcus, and Granulicatella, with the latter especially elevated in late-stage cancer. This dysbiosis, or the abnormal imbalance of bacterial species, is believed to raise levels of ROS associated with DNA damage in the lungs . [29] There have been some significant studies in the latest years that highlighted the importance of cessation smoking among COPD patients. Godtfresen et al. conducted a prospective cohort study involving 19,709 individuals from general population to assess the risk of hospitalization for COPD following whether complete smoking cessation or a reduction in Tabaco smoking over a 14.4 year period. The risk of hospitalization was lower in patients with complete cessation compared to continued smoking (RR = 0.57; 95% CI: 0.33–0.99. On the other side, merely reducing smoking did not show a significant reduction in hospitalization risk compared to persistent smoking (RR = 0.93; 95% CI: 0.73–1.18) . [30] Kanner at al. studied 5,887 participants from the Lung Health Study 1, focusing on current smokers aged 35 to 60 years with mild to moderate COPD. Two groups were given either inhaled ipratropium bromide or a placebo, along with supportive interventions, while the third group received only smoking cessation advice. After five years, the prevalence of respiratory symptoms was significantly reduced in the intervention groups compared to the control group (p < 0.0001). Those who continued smoking had a higher prevalence of symptoms compared to those who quit (p < 0.0001), with symptom improvement apparent within the first year of smoking cessation . [30] Another significant study was conducted by Tonnesen et al., involving a multicenter trial with 370 COPD patients of varying disease severity, aimed at supporting smoking cessation. The study assessed patients using the Saint George's Respiratory Questionnaire at baseline, six months, and twelve months. Participants who quit smoking or reduced their consumption showed improvements in various questionnaire scores, except for the General Reviews 109 'Activity' dimension, which remained unchanged among those who only reduced their smoking . [31] Willemese and col. highlight that in both cross-sectional studies and longitudinal studies is suggested improvement of the respiratory symptoms after smoking cessation, as the most intermitent symptoms (cough, phlegm and wheeze) decrease within 1–2 months after smoking cessation. After smoking cessation the prevalence of cough and wheezing reduces to levels comparable to those of nonsmokers, but the prevalence of phlegm remains slightly elevated . [32] On the other hand, three studies, with smoking cessation periods ranging from 2–6 weeks to 1–12 years, found no change in the prevalence of dyspnea following smoking cessation . [32] In a study conducted by Yong Liu and col., in which the data are collected from 4,135 adults aged 45 and older, years with a history of smoking, showed that patients with COPD that continued to smoke were more likely to have a productive cough, that is consistent with chronic bronchitis. This condition is primarily due to excessive inflammation and hypersecretion of mucus secondary to smoking tobacco products use. Another important conclusion emerged from this study is that the difference in the frequency of dyspnea between current and former smokers was less pronounced . [33] Does quitting smoking improves lung function? Chronic airflow obstruction, identified through spirometry, is the hallmark of COPD. Maximum expiratory flow is determined by resistance in small airways (cm H₂O/L/s) and the lung's elastic recoil, which drives expiratory flow (L/cm H₂O). The interaction of these factors, called the time constant, dictates how quickly the lungs fill and empty. In healthy lungs, this time constant is consistent across breathing rates. However, conditions like emphysema, which increase lung compliance or airway resistance, prolong lung emptying. Spirometry diagnoses fixed airflow limitation by measuring FEV1 and the FEV1/FVC (Forced vital capacity) ratio after bronchodilator use . [34] Quitting smoking presents a crucial opportunity to prevent COPD, as it slows the decline in FEV1, thereby preventing smoke-related respiratory impairment . Additionally, [35] smoking cessation helps prevent other smoking-related lung diseases by positively influencing key inflammatory and remodeling processes in the lungs . [36] Spirometry is essential for assessing airflow limitation, particularly by measuring FEV1. A low FEV1 is predictive of not only an accelerated decline in lung function but also higher rates of morbidity and mortality . [37] Since lung function naturally decreases over time, preventing smoking-related illnesses should begin early in life, though many smoking cessation programs face high relapse rates . [38] Respiratory symptoms alone do not predict changes in lung function, but smokers with airflow obstruction benefit from quitting, regardless of past heavy smoking, advanced age, poor baseline lung function, or airway hyperresponsiveness . [38] About 30% of smokers may not exhibit chronic symptoms or abnormal lung function; however, even these "healthy smokers" experience subtle changes in lung morphology, inflammation, and function. Smoking invariably impacts the lungs, though the severity and extent of these changes vary among individuals . A study by Dhariwal J et [32] al. explored the relationship between smoking and lung function, showing that COPD patients who quit smoking experienced a Internal Medicine 20 4 vol. X I No. 4 - www.srmi.ro2X General Reviews 110 significant but temporary improvement in FEV1 at 6 weeks (184 mL), which persisted somewhat at 12 weeks (81 mL) and was partially maintained after one year. Additionally, both COPD patients who quit smoking and those with normal spirometry who quit smoking showed improvement in lung carbon monoxide transfer factor at 6 weeks . [39] Pezzuto et al. found in their study that reducing cigarette exposure enhances airflow parameters and exercise performance in patients. Data from plethysmography and hemogasanalysis indicated a significant improvement in lung function over a short treatment period (3 months). Increases in vital capacity, FEF 25-75 (Forced Expiratory Flow 25-75%), and FEV1 were accompanied by a decrease in dyspnea index scores and reduced COHb (Carboxyhemoglobin) levels. They also noted that for mid-sized and larger airways, it takes about a year for FEV1 reductions to develop . [35] Spirometric lung age, derived from height and FEV1 using a formula introduced by Morris and Temple, was designed to simplify spirometry data and highlight the effects of smoking to smokers. While some studies have explored whether sharing spirometric lung age influences behavior, little is known about its response to intensive or partial smoking cessation. A study by Iwaoka M. et al. examined changes in lung function in smokers who achieved complete or partial cessation. They found that smokers who fully quit experienced improved lung function within 12 weeks, whereas partial cessation showed no significant short-term benefits . [37] In a systematic review of epidemiological data on smoking and the annual rate of FEV1 decline (beta), Lee PN et al. found that continuing smokers exhibit a beta over 10 mL/yr higher than never-smokers, with beta increasing proportionally to daily cigarette consumption. Ex-smokers have betas comparable to neversmokers, while quitters show only slightly elevated betas. The differences in betas between continuing smokers and quitters do not appear to vary significantly by age or sex but are more pronounced in populations with respiratory diseases compared to the general population . [40] A study by Tashkin et al. analyzed serial spirometric data to assess the sustainability of short-term lung function improvements after smoking cessation. Significant gains were observed within 9 to 12 weeks of abstinence, but these improvements were not maintained at 24 or 52 weeks. The reasons for this decline remain unclear, though substantial long-term benefits may require more than a year of cessation. This study highlights the short-term respiratory benefits of quitting smoking in COPD patients, offering motivation for smokers with COPD to pursue cessation . [41] General Reviews 111 Paul D. Scanlon et al. conducted a five-year prospective trial with 3,926 smokers with mild-to-moderate airway obstruction across 10 North American centers. Participants were assigned to smoking cessation or nonintervention groups, with annual lung function assessments. Quitters experienced a 47 mL (2%) FEV1 improvement in the first year, and their annual FEV1 decline over four years was half that of continuing smokers. Greater initial airway responsiveness and lower lung function predicted larger first-year improvements, while younger participants and women showed better outcomes overall. However, women who continued smoking had greater FEV1 decline than men . [38] The ECLIPSE study, led by Vestbo J and colleagues, tracked 2,164 COPD patients over three years with detailed assessments at baseline and multiple follow-ups. Testing included CT scans, spirometry, 6MWT (SixMinute Walk Test), and biomarker sampling. FEV1 decline showed considerable variability, averaging 33 mL/year—lower than expected. Key contributors to faster decline were continued smoking (21 ± 3.8 mL/year), CT-defined emphysema (13 ± 4.2 mL/year), and bronchodilator reversibility (17 ± 4.2 mL/year) . [42] Smoking cessation is the most effective strategy to slow the accelerated decline in lung function and improve respiratory symptoms in smokers with COPD . When [41] counseling smokers to quit, they may argue they are too old to benefit, smoke too much to quit, or have already caused irreversible lung damage. However, studies strongly refute these claims. Heavy smokers gain the most from quitting and risk the most by continuing. Older smokers see similar benefits to younger ones in slowing lung function decline. Those with the worst lung function experience the fastest deterioration if they keep smoking, making quitting especially crucial for them . [38] An optimal smoking cessation strategy today should include a comprehensive support program, whether individual or group-based, combined with a first-line pharmacological smoking cessation agent, such as NRT (Nicotine Replacement Therapy), varenicline, or bupropion SR for three months. If relapse occurs, retreatment should be offered . [43] The value of CT for the diagnosis of smoking related comorbidities COPD is a syndrome that includes a diverse range of conditions, all characterized by chronic airflow obstruction, with varying contributions from emphysema, small-airway disease, and chronic bronchitis. This airflow limitation is irreversible and results from different combinations of central and peripheral airway damage as well as emphysematous changes, which occur due to the destruction of alveolar structures from prolonged exposure to harmful particles or gases . [44] Among all risk factors, smoking is the primary known contributor to the development of COPD. However, the degree of chronic airflow obstruction that develops varies significantly among smokers . Since not all smokers will [45] develop COPD, predictive factors like the extent of low-attenuation areas in individuals without airway obstruction could help identify those at risk of developing the disease. For instance, a diagnosis of COPD via HRCT (HighResolution Computed Tomography) can be made by detecting diffuse, scattered lowattenuation areas in the lung parenchyma . [46] This is crucial because stabilizing the disease through smoking cessation is a key aspect of COPD management . [47] Early diagnosis of COPD allows for earlier treatment and improved prevention of Internal Medicine 20 4 vol. X I No. 4 - www.srmi.ro2X General Reviews 118 duration and amount of smoking increasing the risk of microvascular complications, while quitting smoking improves nephropathy . [80] When it comes to mortality, a study by Chi et al. revealed a synergistic relationship between smoking and diabetes, with the combined effect significantly increasing the risk of death compared to either condition alone . [81] Overweight or obesity are the strongest predictors of diabetes, with poor diet, smoking, abstinence from alcohol, and low levels of physical activity also independently associated with increased diabetes risk . [34] The risk is higher for type 2 diabetes than type 1, which is relatively rare in the studied age groups . On average, 20% of people with '[34] T2DM and 30% of those with type 1 diabetes mellitus (T1DM) are smokers, with smoking more prevalent among men and individuals from lower socioeconomic groups . [78] Several prospective studies have shown that smoking increases the risk of type 2 diabetes in both men and women . Furthermore, the [34] microvascular complications are more frequent among women than among men with diabetes . Although men with diabetes [80] consistently have a higher prevalence of smoking compared to women, smoking rates among women with diabetes have been rising, similar to trends in the general population . A study by Thomas Ernst Doner [78] et al. noted a significant increase in smoking prevalence among women in Austria over a seven-year period, particularly among those with chronic diseases, older age, lower education, and migration backgrounds . [82] Another study highlighted that smoking was widespread among young female T1DM patients and middle-aged T1DM and T2DM patients, warranting targeted smoking cessation campaigns. Smoking in these patients was linked to poor glycemic control and microalbuminuria, independent of other factors . [83] Research on patients with type 1 diabetes has reported negative effects of tobacco use on albuminuria and renal function, with smoking accelerating the progression of renal disease in those with type 2 diabetes . The study by [34] Nilsson PM et al. found that microalbuminuria is more common among smoking diabetics than nonsmokers and that smoking contributes to the risk factors associated with microalbuminuria and nephropathy in both T1DM and T2DM . [83] In diabetes care, smoking cessation is essential for improving glycemic control and reducing the risk of complications. The increased risk of diabetes decreases five years after quitting smoking and normalizes after 20 years . A study by Wannamethee et '[34] al. found that cigarette smoking significantly increases diabetes risk, even after adjusting for age, BMI, and other potential confounders. The benefits of quitting smoking become apparent after five years, General Reviews 119 with the risk reverting to that of neversmokers only after 20 years. Despite significant weight gain and a higher risk of diabetes in men who quit smoking within the first five years, the long-term benefits of smoking cessation outweigh the early adverse effects of weight gain . [84] Impact on quality of life Despite a significant decline in tobacco use in many countries, smoking remains the leading health risk linked to early-stage disease and death. Several studies have explored the connection between smoking and healthrelated quality of life (HRQoL), showing that cigarette consumption is associated with lower QoL and mental well-being . The link between [85] smoking and mental health is not so clear. While most smokers express a desire to quit, many continue because they believe smoking offers mental health benefits. Both quantitative and qualitative studies show that regular smokers use cigarettes to cope with emotional issues, depression, anxiety, stabilize mood, relax, and relieve stress . In [86] fact smoking may worsen mental health through neuroadaptations from chronic use, causing nicotine withdrawal symptoms such as anxiety, depression, and irritability. In these cases, quitting smoking could improve mental health instead of worsening it . [87] The firm belief among some smokers that quitting will negatively impact their quality of life presents a major obstacle to cessation. Providing information about the long-term improvements in life satisfaction and quality of life after quitting could offer valuable insights for clinicians working with smokers concerned about the consequences of quitting. This knowledge could also be used to motivate and educate smokers on a larger scale, such as through media campaigns . Cross-sectional [88] studies have revealed that smokers tend to have lower HRQoL compared to non-smokers. Additionally, findings from several longitudinal studies suggest that individuals who smoked at baseline experienced worse physical HRQoL at follow-up than those who had never smoked. Furthermore, those who continued smoking from baseline to follow-up reported a decline in HRQoL at follow-up . [89] Smoking cessation interventions, like aerobic exercise, may also improve QoL. Exercise has immediate benefits for psychological wellbeing, such as reducing cravings and withdrawal symptoms. Additionally, regular exercise provides well-documented benefits for QoL, regardless of smoking status . The [90] impact of tobacco on smokers' HRQoL can vary based on factors like the number of cigarettes smoked and nicotine dependence. For example, heavy smokers tend to have lower HRQoL scores. Dependent smokers report worse quality of life than non-dependent smokers. Other factors, such as age of smoking initiation, age of quitting, stages of change, and quit attempts, also play a role. Smokers who start before 15 have lower HRQoL, and quitting at an older age is linked to lower HRQoL scores. Smokers near quitting report worse physical health, while those not intending to quit show worse mental health. Additionally, smokers who unsuccessfully attempted to quit tend to have poorer HRQoL . [91] Tobacco smoking remains a leading cause of COPD, with passive smoking also contributing to respiratory symptoms and disease progression. Management of COPD focuses on clinical goals like preventing disease progression and minimizing symptoms, as well as improving health-related quality of life, including exercise tolerance and emotional well-being. Health status, functional status, and quality of life are often used interchangeably to describe this domain, with Internal Medicine 20 4 vol. X I No. 4 - www.srmi.ro2X General Reviews 120 HRQoL being crucial for assessing the impact of chronic diseases like COPD . The HRQoL of [92] COPD patients is influenced by multiple factors, including comorbidities like cardiovascular disease, diabetes, and osteoporosis, as well as risk factors such as smoking, low body weight, and inactivity. HRQoL measures the impact of disease on daily functioning. Current COPD treatment protocols focus not only on symptom management but also on improving HRQoL. Improving quality of life involves reducing exacerbations, enhancing lung function, and encouraging smoking cessation, weight control, and physical activity . [93] As such, promoting smoking cessation among COPD patients is a critical priority for healthcare professionals. Given the chronic nature of COPD, home healthcare clinicians often have frequent interactions with patients, providing numerous opportunities to educate them about quitting smoking. It is essential for clinicians to feel confident in assessing patients' readiness to quit, as these discussions are crucial for encouraging cessation and improving QoL . [94] Conclusions Smoking cessation remains the most effective intervention to slow disease progression and improve outcomes in COPD patients. This review highlights its significant benefits across multiple domains. By addressing the physiopathology of COPD, we have underscored how smoking cessation mitigates airway inflammation, reduces oxidative stress, and preserves lung function. Cessation leads to measurable improvements in respiratory symptoms, reducing dyspnea, cough, and exacerbation frequency. Additionally, its positive impact extends beyond the respiratory system, lowering the risk of cardiovascular disease, diabetes, and lung cancer - common comorbidities in COPD patients. Advances in imaging, particularly CT, have enhanced the early diagnosis of smokingrelated complications, reinforcing the importance of quitting smoking to prevent further structural lung damage. Moreover, improved lung function following cessation translates into better exercise capacity, reduced hospitalizations, and overall improvements in daily activities. Patients report enhanced physical and mental well-being, with decreased anxiety and depression levels, highlighting the far-reaching impact of smoking cessation on quality of life. Given the overwhelming evidence, healthcare providers must prioritize smoking cessation strategies as a cornerstone of COPD management. Acknowledgement This article was published with the support provided by the GRANT AGREEMENT NUMBER 101008139, under the EUREST – RISE – General Reviews 121 H2020 – MSCA – RISE – 2020 project, implemented in Romania by the 'Aer Pur Romania' Association. Conflict of interest: There was no conflict of interest. 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