A-Level Biology: Effects of Smoking on the Respiratory System | A-Level 生物：吸烟对呼吸系统的影响

📚 A-Level Biology: Effects of Smoking on the Respiratory System | A-Level 生物：吸烟对呼吸系统的影响

Smoking remains one of the most significant preventable causes of disease and premature death worldwide. This article examines the biological mechanisms by which tobacco smoke damages the respiratory system, a core topic in the CIE A-Level Biology syllabus. Understanding these effects requires knowledge of respiratory anatomy, the body’s defence mechanisms, and the cellular responses to toxic compounds found in cigarette smoke.

吸烟仍然是全球范围内最重要的可预防的疾病和过早死亡原因之一。本文探讨了烟草烟雾损害呼吸系统的生物学机制，这是 CIE A-Level 生物学课程的核心主题。理解这些影响需要了解呼吸系统解剖学、人体防御机制以及细胞对香烟烟雾中有毒化合物的反应。

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1. Composition of Cigarette Smoke | 香烟烟雾的成分

Cigarette smoke contains over 7,000 chemical compounds, of which at least 70 are known carcinogens. The major harmful components include tar, nicotine, carbon monoxide, and various irritant gases such as formaldehyde, ammonia, and nitrogen oxides. These substances can be categorised into particulate matter (tar and solid particles) and gaseous components, each with distinct pathological effects on the respiratory tract.

香烟烟雾含有超过7000种化合物，其中至少有70种是已知的致癌物。主要有害成分包括焦油、尼古丁、一氧化碳以及各种刺激性气体，如甲醛、氨和氮氧化物。这些物质可分为颗粒物（焦油和固体颗粒）和气态成分，每种对呼吸道都具有不同的病理效应。

Key components and their targets:

• Tar — a sticky residue that coats the airways, paralyses cilia and stimulates excessive mucus secretion.
• Nicotine — an addictive alkaloid that causes vasoconstriction and increases heart rate; it also inhibits the normal function of alveolar macrophages.
• Carbon monoxide — binds to haemoglobin with approximately 250 times greater affinity than oxygen, reducing oxygen-carrying capacity.
• Oxidising agents — free radicals that damage cell membranes via lipid peroxidation and inactivate α₁-antitrypsin.

主要成分及其作用靶点：

• 焦油 — 一种粘稠的残留物，覆盖在气道表面，麻痹纤毛并刺激过量黏液分泌。
• 尼古丁 — 一种成瘾性生物碱，引起血管收缩并增加心率；同时抑制肺泡巨噬细胞的正常功能。
• 一氧化碳 — 与血红蛋白的结合能力约为氧气的250倍，从而降低血液携氧能力。
• 氧化剂 — 自由基，通过脂质过氧化损伤细胞膜，并使α₁-抗胰蛋白酶失活。

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2. The Respiratory Defence System | 呼吸系统防御机制

To understand smoking’s pathological effects, one must first appreciate the normal defence mechanisms of the respiratory system. The nasal cavity filters large particles; the trachea and bronchi are lined by ciliated pseudostratified columnar epithelium containing goblet cells that secrete mucus. Goblet cells and submucosal glands produce a mucus layer approximately 5-10 μm thick that traps inhaled particles. The coordinated beating of cilia moves this mucus layer upward toward the pharynx, a process known as the mucociliary escalator, clearing debris at a rate of approximately 1-2 cm per minute.

要理解吸烟的病理效应，首先必须了解呼吸系统的正常防御机制。鼻腔过滤大颗粒；气管和支气管内衬有纤毛假复层柱状上皮，其中含有分泌黏液的杯状细胞。杯状细胞和黏膜下腺体产生约5-10 μm厚的黏液层，用以捕获吸入的颗粒物。纤毛协调一致的摆动将该黏液层向上推向咽部，这一过程称为黏液纤毛升降机，以每分钟约1-2 cm的速度清除碎屑。

Alveolar macrophages serve as the second line of defence, phagocytosing particles that escape mucociliary clearance and reach the alveoli. These professional phagocytes release cytokines that recruit neutrophils and other immune cells when necessary. The integrity of the alveolar epithelium and the surfactant layer further contribute to the defence against inhaled pathogens and particulates. Smoking disrupts each of these mechanisms in a cumulative and, in many cases, irreversible manner.

肺泡巨噬细胞构成第二道防线，吞噬那些逃过黏液纤毛清除并到达肺泡的颗粒。这些专职吞噬细胞在必要时释放细胞因子，招募中性粒细胞和其他免疫细胞。肺泡上皮的完整性和表面活性物质层进一步有助于防御吸入的病原体和颗粒物。吸烟会以累积性的、且在多数情况下不可逆的方式破坏上述每一种机制。

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3. Effects on Cilia and Mucociliary Clearance | 对纤毛和黏液纤毛清除的影响

The gaseous phase of cigarette smoke, particularly acrolein and formaldehyde, directly impairs ciliary function. Within minutes of exposure, ciliary beating frequency decreases significantly. Chronic exposure leads to ciliary paralysis and ultimately loss of ciliated cells, which are replaced by mucus-secreting goblet cells — a process called squamous metaplasia. The number of goblet cells increases, resulting in excessive mucus production, while the functional cilia population declines. This imbalance creates the characteristic “smoker’s cough”: the mucociliary escalator fails, and mucus accumulates, requiring coughing to clear.

香烟烟雾的气相部分，特别是丙烯醛和甲醛，直接损害纤毛功能。暴露数分钟内，纤毛摆动频率即显著降低。长期暴露导致纤毛麻痹，并最终使纤毛细胞丧失，被分泌黏液的杯状细胞取代——这一过程称为鳞状化生。杯状细胞数量增加，导致黏液过量产生，而功能性纤毛种群减少。这种不平衡产生了典型的“吸烟者咳嗽”：黏液纤毛升降机失效，黏液积聚，需通过咳嗽来清除。

Histological changes include hypertrophy of submucosal glands and hyperplasia of goblet cells (Reid index increases). The mucus produced by smokers is also thicker and more viscous, further compromising clearance. Cigarette smoke reduces the number of ciliated cells per unit area of bronchial epithelium from approximately 50-70% in non-smokers to less than 20% in long-term smokers. This loss of structural integrity predisposes individuals to recurrent respiratory infections.

组织学改变包括黏膜下腺体肥大和杯状细胞增生（Reid指数升高）。吸烟者产生的黏液也更稠厚、黏滞度更高，进一步损害清除功能。香烟烟雾使支气管上皮单位面积的纤毛细胞比例从非吸烟者的约50-70%降至长期吸烟者的不足20%。这种结构完整性的丧失使个体易患反复呼吸道感染。

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4. Damage to the Alveoli and Gas Exchange | 对肺泡和气体交换的损伤

Chronic smoking leads to destruction of alveolar walls through a combination of direct toxicity and protease-antiprotease imbalance. The lungs contain approximately 480 million alveoli, providing a surface area of about 70-100 m², roughly the size of a tennis court. Each alveolus is surrounded by a dense network of pulmonary capillaries, forming the respiratory membrane — the barrier for gas exchange, which is only 0.5-1 μm thick. Smoking progressively destroys this delicate architecture.

慢性吸烟通过直接毒性和蛋白酶-抗蛋白酶失衡的综合作用导致肺泡壁破坏。肺内约有4.8亿个肺泡，提供约70-100 m²的表面积，大致相当于一个网球场的大小。每个肺泡周围环绕着密集的肺毛细血管网，形成呼吸膜——气体交换的屏障，其厚度仅为0.5-1 μm。吸烟进行性破坏这一精密结构。

Two key mechanisms are involved. First, cigarette smoke stimulates neutrophils and alveolar macrophages to release elastase and other proteases. Second, oxidants in smoke inactivate α₁-antitrypsin, the principal inhibitor of elastase. The resulting protease excess causes degradation of elastin and other structural proteins in the alveolar septa. This process is the hallmark of pulmonary emphysema — permanent enlargement of air spaces distal to the terminal bronchiole with destruction of alveolar walls. The loss of elastic recoil and surface area reduces the efficiency of gas exchange and causes air trapping, leading to hyperinflation of the lungs.

涉及两个关键机制。第一，香烟烟雾刺激中性粒细胞和肺泡巨噬细胞释放弹性蛋白酶和其他蛋白酶。第二，烟雾中的氧化剂使α₁-抗胰蛋白酶失活，而该酶是弹性蛋白酶的主要抑制剂。由此产生的蛋白酶过量导致肺泡间隔中弹性蛋白和其他结构蛋白的降解。这一过程是肺气肿的标志——终末细支气管以远的气腔永久性增大，伴有肺泡壁的破坏。弹性回缩力和表面积的丧失降低了气体交换效率并导致气体陷闭，引起肺过度充气。

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5. Inflammatory Response and Chronic Bronchitis | 炎症反应与慢性支气管炎

Chronic bronchitis is defined clinically as a chronic productive cough lasting at least three months per year for two consecutive years. Smoking-induced inflammatory changes in the airways are central to this condition. Irritants in smoke trigger an inflammatory response characterised by infiltration of neutrophils, macrophages, and CD8⁺ T-lymphocytes into the bronchial wall. These immune cells release pro-inflammatory cytokines such as TNF-α, IL-8, and leukotriene B₄, which amplify the inflammatory cascade.

慢性支气管炎的临床定义是连续两年中每年至少持续三个月的慢性咳嗽咳痰。吸烟引起的气道炎症性改变是该病的核心。烟雾中的刺激物触发炎症反应，其特征是中性粒细胞、巨噬细胞和CD8⁺ T淋巴细胞向支气管壁的浸润。这些免疫细胞释放促炎细胞因子，如TNF-α、IL-8和白三烯B₄，从而放大炎症级联反应。

Chronic inflammation causes structural remodelling of the airways, including smooth muscle hypertrophy, fibrosis, and narrowing of the bronchial lumen. Mucous gland hyperplasia increases the Reid index, and the excessive mucus further obstructs airflow. These changes result in increased airway resistance, particularly during expiration, leading to air trapping and ventilation-perfusion mismatch. The partial pressure of oxygen in arterial blood (PaO₂) falls, while partial pressure of carbon dioxide (PaCO₂) rises, reflecting impaired alveolar ventilation.

慢性炎症导致气道结构重塑，包括平滑肌肥大、纤维化和支气管管腔狭窄。黏液腺增生使Reid指数升高，过多的黏液进一步阻碍气流。这些改变导致气道阻力增加，尤其在呼气时，引起气体陷闭和通气-灌注比例失调。动脉血氧分压（PaO₂）下降，而二氧化碳分压（PaCO₂）升高，反映肺泡通气功能受损。

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6. Effects on Alveolar Macrophages and Immunity | 对肺泡巨噬细胞和免疫的影响

Alveolar macrophages are the primary phagocytic cells in the alveolar space, responsible for clearing inhaled pathogens and particulate matter. Cigarette smoke profoundly impairs their function. Nicotine and other components inhibit phagocytosis, reduce bactericidal activity, and suppress the production of pro-inflammatory cytokines in response to infection. Studies show that macrophages from smokers have reduced expression of surface receptors such as Fcγ receptors and complement receptors, which are crucial for opsonisation and microbial recognition.

肺泡巨噬细胞是肺泡腔内的主要吞噬细胞，负责清除吸入的病原体和颗粒物。香烟烟雾严重损害其功能。尼古丁和其他成分抑制吞噬作用，降低杀菌活性，并抑制感染时促炎细胞因子的产生。研究表明，吸烟者体内的巨噬细胞表面受体表达减少，如Fcγ受体和补体受体，而这些受体对于调理作用和微生物识别至关重要。

Smokers also exhibit impaired T-cell function and reduced activity of natural killer (NK) cells. This combined immunodeficiency explains the increased susceptibility of smokers to respiratory infections, including influenza, tuberculosis, and bacterial pneumonia. Moreover, the chronic inflammatory state induced by smoking disrupts the normal balance between Th1 and Th2 immune responses, contributing further to tissue damage and remodelling within the lungs.

吸烟者的T细胞功能和自然杀伤（NK）细胞活性也降低。这种联合免疫缺陷解释了为什么吸烟者更容易罹患呼吸道感染，包括流感、结核病和细菌性肺炎。此外，吸烟诱发的慢性炎症状态破坏了Th1和Th2免疫反应之间的正常平衡，进一步加剧肺内的组织损伤和重塑。

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7. Cancer Development | 癌症的发生

Lung cancer is the leading cause of cancer-related death globally, and approximately 85-90% of cases are attributable to smoking. Carcinogens in tobacco smoke, particularly polycyclic aromatic hydrocarbons (such as benzo[a]pyrene) and nitrosamines (such as NNK), form DNA adducts — covalent bonds between the carcinogen and DNA bases. If these adducts are not repaired by nucleotide excision repair mechanisms, they cause mutations during DNA replication.

肺癌是全球癌症相关死亡的首要原因，约85-90%的病例归因于吸烟。烟草烟雾中的致癌物，特别是多环芳烃（如苯并[a]芘）和亚硝胺（如NNK），与DNA碱基形成加合物——即致癌物与DNA碱基之间的共价键。如果这些加合物未被核苷酸切除修复机制修复，就会在DNA复制过程中引起突变。

A characteristic feature of smoking-related lung cancer is the presence of G-to-T transversion mutations in the TP53 tumour suppressor gene and KRAS oncogene. The mutation spectrum serves as a “molecular fingerprint” of tobacco exposure. The development of lung cancer involves multiple genetic and epigenetic alterations accumulated over time — a multistep process of initiation, promotion, and progression. Ciliated epithelial cells and basal cells may undergo dysplasia, carcinoma in situ, and eventually invasive carcinoma. The main histological types associated with smoking include squamous cell carcinoma and small cell lung carcinoma, which arise from the metaplastic epithelium in the central airways.

吸烟相关肺癌的一个特征性表现是TP53肿瘤抑制基因和KRAS癌基因中的G→T颠换突变。这种突变谱是烟草暴露的“分子指纹”。肺癌的发生涉及随时间的推移而积累的多重遗传学和表观遗传学改变——即启动、促进和进展的多步骤过程。纤毛上皮细胞和基底细胞可能经历不典型增生、原位癌，最终发展为浸润性癌。与吸烟相关的主要组织学类型包括鳞状细胞癌和小细胞肺癌，两者均起源于中央气道的化生上皮。

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8. Chronic Obstructive Pulmonary Disease (COPD) | 慢性阻塞性肺疾病（COPD）

COPD is a progressive, largely irreversible disease characterised by persistent airflow limitation. It encompasses two main pathological entities: chronic bronchitis (affecting primarily the airways) and emphysema (affecting primarily the alveoli). Smoking is the single most important risk factor for COPD, accounting for approximately 80-90% of cases in developed countries. The disease develops over decades of exposure, following the so-called “British hypothesis” — that chronic mucus hypersecretion and reduced mucociliary clearance lead to recurrent infection and progressive airway obstruction.

COPD是一种进行性、且大多不可逆的疾病，其特征是持续的空气流受限。它包含两个主要的病理实体：慢性支气管炎（主要影响气道）和肺气肿（主要影响肺泡）。吸烟是COPD最重要的单一危险因素，占发达国家病例的约80-90%。该病经过数十年的暴露逐渐发展，遵循所谓的“英国假说”——即慢性黏液过度分泌和黏液纤毛清除功能降低导致反复感染和进行性气道阻塞。

Physiologically, COPD is characterised by:

• Reduced FEV₁ (forced expiratory volume in 1 second) — from ly 4L in healthy young adults to less than 1.5L in severe disease
• Decreased FEV₁/FVC ratio (normally greater than 0.7; in COPD, often below 0.6)
• Increased residual volume and functional residual capacity due to air trapping
• Reduced diffusing capacity of the lungs for carbon monoxide (DLCO), reflecting alveolar destruction

从生理学角度，COPD的特征包括：

• FEV₁（第一秒用力呼气量）降低——从健康年轻人的约4L降至重度患者的不到1.5L
• FEV₁/FVC比值降低（正常大于0.7；COPD患者常低于0.6）
• 残气量和功能残气量增加，由于气体陷闭所致
• 肺一氧化碳弥散量（DLCO）降低，反映肺泡破坏

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9. Systemic Effects Relevant to Respiratory Function | 与呼吸功能相关的全身性效应

Although this article focuses on the respiratory system, smoking’s effects on other systems indirectly compromise respiratory function. Carbon monoxide binds to haemoglobin to form carboxyhaemoglobin (COHb), which reduces the oxygen-carrying capacity of the blood. In chronic smokers, COHb levels typically reach 5-10%, compared to less than 1% in non-smokers. Furthermore, carbon monoxide causes a leftward shift of the oxyhaemoglobin dissociation curve, impairing oxygen release to tissues, although chronic hypoxia partially compensates via increased 2,3-BPG levels.

尽管本文聚焦于呼吸系统，但吸烟对其他系统的影响也会间接损害呼吸功能。一氧化碳与血红蛋白结合形成碳氧血红蛋白（COHb），降低血液携氧能力。在慢性吸烟者中，COHb水平通常达到5-10%，而非吸烟者不到1%。此外，一氧化碳使氧合血红蛋白解离曲线左移，损害氧气向组织的释放，尽管慢性缺氧通过增加2,3-二磷酸甘油酸（2,3-BPG）水平部分代偿。

Nicotine-induced vasoconstriction of the pulmonary vasculature increases pulmonary arterial pressure, contributing to the development of cor pulmonale — right ventricular hypertrophy and failure secondary to pulmonary hypertension, a late complication of COPD. Smoking also reduces the levels of circulating antioxidants such as vitamin C and glutathione, diminishing the body’s capacity to neutralise the oxidative burden imposed by cigarette smoke. These systemic effects reinforce the need to view smoking as a multi-organ threat rather than a purely respiratory problem.

尼古丁引起的肺血管收缩使肺动脉压升高，有助于肺源性心脏病的发展——即继发于肺动脉高压的右心室肥大和衰竭，这是COPD的晚期并发症。吸烟还降低循环中的抗氧化剂水平，如维生素C和谷胱甘肽，削弱了机体中和香烟烟雾所施加的氧化负担的能力。这些全身性效应强化了应将吸烟视为多器官威胁，而不仅仅是呼吸系统问题的观点。

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10. Preventive and Therapeutic Strategies | 预防和治疗策略

Given the gravity of smoking-related respiratory disease, prevention is paramount. Smoking cessation is the single most effective intervention to slow the decline in lung function. Within weeks of quitting, ciliary function begins to recover and excess mucus production decreases. Some improvements, such as reduced coughing and improved immune function, occur within months; however, DNA damage in the bronchial epithelium may persist for years. Clinically, smoking cessation together with pharmacological therapies — such as bronchodilators (β₂-agonists and antimuscarinics), inhaled corticosteroids, and supplemental oxygen — form the pillars of COPD management.

鉴于吸烟相关呼吸系统疾病的严重性，预防至关重要。戒烟是减缓肺功能下降最有效的单一干预措施。戒烟后数周内，纤毛功能开始恢复，过量黏液产生减少。一些改善，如咳嗽减轻和免疫功能增强，在数月内即可出现；然而，支气管上皮中的DNA损伤可能持续数年。在临床上，戒烟联合药物治疗——如支气管扩张剂（β₂受体激动剂和抗胆碱能药物）、吸入性糖皮质激素和辅助供氧——构成COPD管理的支柱。

The A-Level syllabus also emphasises public health measures: educational campaigns, taxation on tobacco products, smoke-free policies in public spaces, and the availability of nicotine replacement therapy (NRT) and e-cigarettes as harm-reduction strategies. At the cellular level, research into antioxidants, protease inhibitors, and the restoration of epithelial ion transport offers hope for future therapies to mitigate the damage caused by smoking.

A-Level课程还强调公共卫生措施：教育宣传、烟草产品征税、公共场所无烟政策，以及提供尼古丁替代疗法（NRT）和电子烟作为减害策略。在细胞水平上，针对抗氧化剂、蛋白酶抑制剂和上皮离子转运恢复的研究为未来缓解吸烟所造成损伤的疗法带来了希望。

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