Overview of pulmonary Fibrosis

What is pulmonary fibrosis?

Pulmonary fibrosis (PF) is a chronic lung disease in which scar tissue replaces normal lung tissue. With time, this leads to a decline in lung function and respiratory failure.¹ Patients with PF usually suffer from more than one disease. Common comorbidities include gastroesophageal reflux disease (GERD)² and depression.³ With disease progression, patients may develop heart failure and risk of fatal cardiovascular incidents.⁴

What are the causes and risk factors for pulmonary fibrosis?

The most common form of PF is idiopathic pulmonary fibrosis (IPF).¹ As the name suggests, IPF has no known cause, although some risk factors are associated with the development and progression of this disease. These include smoking, age over 60 years, male sex, and family history of pulmonary fibrosis.⁵

Smoking as a risk factor for pulmonary fibrosis

Why is smoking bad for your lungs?

Tobacco smoke is a mixture of over 5,000 compounds, many of which are responsible for the carcinogenic, respiratory, and cardiovascular effects of cigarette smoking. Some of the toxic chemicals in tobacco smoke are as follows:⁶

• Benzene– benzene is a carcinogenic compound⁷ that contributes to a significant portion of smoking-induced leukaemia deaths.⁸
• Formaldehyde– formaldehyde is a well-known airway irritant and a cause of upper respiratory system cancers in smokers.⁹
• Carbon monoxide– a product of incomplete burning of organic matter,¹⁰ carbon monoxide in acute exposure causes “flu-like” symptoms such as fatigue, vomiting, and headache.¹¹
• Cadmium– cadmium exerts its toxicity via binding to endogenous antioxidants such as glutathione and by depleting them increases the generation of reactive oxygen species that cause oxidative stress and damage to the lung tissue.¹²
• Hydrogen cyanide– a potent mitochondrial poison that inhibits cytochrome oxidase- an enzyme responsible for cellular oxygen utilisation.¹³
• Nitrogen oxides– particularly nitrogen oxide (NO) and nitrogen dioxide (NO₂). The latter is a strong irritant to mucosal linings due to the formation of mixtures of acids on contact with mucosal water.¹⁴

Tobacco smoke contains not only harmful chemicals but also microscopic dust particles that are easily nebulised and upon inhalation precipitate in the smallest airways and alveoli. Both toxic chemicals and microscopic dust particles from cigarette smoke contribute to the process of lung tissue scarring and PF in chronic smokers.¹⁵

Mechanism of smoking-induced lung damage and fibrosis

The respiratory system has a complex role in maintaining host defensive barriers against external harm. These barriers comprise mucus secretion, mucociliary clearance, local immune cells, antibodies, signalling molecules, and the tightly packed respiratory epithelium. Smoking decreases the effectiveness of these defensive mechanisms, causes direct irritation and inflammation in lung tissue, and increases susceptibility to respiratory infections in smokers.

The chemical constituents and microscopic dust particles in tobacco smoke cause infiltration of immune cells in lung parenchyma, release of inflammatory signalling molecules, activation of fibroblasts, formation of new blood vessels, and tissue repair with the deposition of fibrous (scar) tissue. Chronic exposure to tobacco smoke, both in active and passive smokers, effectively leads to fibrosis of the lungs.¹⁶

Development and progression of pulmonary fibrosis in smokers

Smoking is the most strongly associated risk factor for the development of IPF as the majority of patients with IPF are either current or ex-smokers.¹⁷ Cigarette smoking is associated with earlier onset of IPF as well as earlier mortality in IPF patients who smoke.¹⁸ It is therefore crucial to understand the methods for smoking cessation as part of the complex treatment regimen for PF patients.

Smoking cessation in the management of pulmonary fibrosis

Benefits of smoking cessation

In one study on the benefits of short-term smoking cessation, participants showed increased pulmonary function (assessed via spirometry) and decreased levels of markers for systemic inflammation.¹⁹ Short-term smoking cessation is well known to reduce the risk of cardiovascular disease by decreasing levels of markers for endothelial damage such as the adhesion molecule ICAM-1.²⁰ Long-term smoking cessation has shown to slow down the development of pulmonary arterial hypertension,²¹ which is a leading cause of heart-related complications of PF, and also reduces the symptoms of GERD, improving health-related quality of life in patients with PF as well as preventing GERD-related lung scarring responsible for further progression of PF.²²

Therapeutic approaches for smoking cessation

Smoking cessation is one of the best ways to improve lung health in patients with chronic lung diseases. There are a variety of methods to stop smoking:

• Vapes and heated tobacco products (HTP) 
• Nicotine-replacement therapy (NRT)
• Prescription medicines
• Cognitive behavioural therapy (CBT)

As discussed above, the primary cause of lung damage in tobacco smokers is the smoke itself. In order to reduce these effects while keeping the nicotine, several alternatives of nicotine replacement have been widely implemented as OTC products. These include chewing gums, sprays, patches, pouches, etc. It is important to have a good understanding of the proper use of NRT products. Combining several NRT products with or without concomitant tobacco may cause nicotine overdose. Symptoms of overdose include nausea/vomiting, muscle cramps, and seizures, and may negatively affect adherence to NRT treatment. Nicotine gums are a simple and convenient option for smokers and they are well-perceived by the public;²³ however, there is a misconception that nicotine gums should be used like any other chewing gum. There is a specific way to take nicotine gums– first, the gum should be chewed slowly until a tingling sensation appears in the mouth. That’s when nicotine gets released from the gum. Then, the nicotine gum should be “parked” between the inner lining of the cheek and the gum to allow nicotine to absorb through the oral mucosa; then this “chew” and “park” process should be repeated until the tingling sensation disappears.²⁴ This not only maximises absorption of nicotine but also reduces side effects of excessive nicotine swallowing, such as heartburn and stomach ache. Patients should be well informed by their healthcare provider of the safe use of NRT products.²⁵

During the last few years, the use of HTP and vapes has dramatically increased due to the marketing of smoke-free nicotine products. The exact public health benefits of these devices are debatable. While they reduce the rate of tobacco smoking, it is at the expense of increased nicotine use in both former smokers and non-smokers, becoming especially popular in the youth.²⁶ Nevertheless, there is strong evidence that switching from traditional cigarette smoking to such alternatives does have benefits for long-term lung health.²⁶ HTP mimics traditional cigarettes but instead of burning tobacco, these devices have an incorporated heating system that allows for nicotine delivery without combustion, thus releasing practically no smoke.²⁷ Unfortunately, no studies have shown e-cigarettes to help smoking cessation.²⁸ Vapes on the other hand are tobacco-free devices that contain a liquid mixture of nicotine, glycerin, and propylene glycol that turn into an aerosol upon inhalation.²⁶ Unlike HTP, vaping does appear to help smokers quit and has a good safety profile compared to traditional cigarettes.²⁹ This should not encourage non-smokers to start vaping as there are some health concerns in this regard. Propylene glycol contained in vaping liquid has an irritating effect on the lining of the respiratory system, causing bronchospasms. In addition, a fraction of aerosolized propylene glycol under heat converts into formaldehyde, a well-known carcinogen.³⁰

Some prescription medicines are used to help people quit smoking. The most common medicines for this purpose are the antidepressants bupropion and varenicline. They work by affecting neurochemical pathways in the brain, leading to reduced cravings for tobacco. Both medicines affect nicotine dependence versus placebo, but varenicline is superior to bupropion in improving abstinence, suggesting a stronger effect on smoking cessation.³¹ These medicines should however be prescribed by the appropriate healthcare professionals.

Cognitive behavioural therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of smoking addiction by helping affected people realise the triggers of their nicotine cravings and try finding alternative behaviours to replace smoking.³² CBT should be used in conjunction with other smoking cessation methods to maximise long-term results.³³ It is important to have a specific approach with every person when performing CBT. Some people have specific reasons for taking up smoking– some are afraid of gaining weight after quitting; others may have a stressful lifestyle and have developed a coping mechanism for managing anxiety through smoking; some people have integrated smoking into their lives as small “rituals” that they are used to having on a daily basis. Depending on the level of attachment a person has developed to the habit of smoking, specialists should approach each case individually.

Strategies for prevention of smoking for at-risk populations

• Educational campaigns for raising awareness– large campaigns for raising awareness of the public harm of tobacco smoking are a common national priority combining the efforts of healthcare, social, and educational organisations. It is important to raise awareness not only of the direct harm of smoking but also of the risk of smoking in pregnancy, the risk for passive smokers, the risk for substance abuse in children, etc.
• National smoking prevention programmes– given the enormous socio-economic and healthcare impact smoking has, many countries have developed national programmes for smoking prevention. Some countries have adopted the strategies of banning tobacco product advertising, printing written and pictorial health warnings of smoking complications and risk of death on cigarette packs, developing anti-tobacco initiatives, raising taxes for tobacco products, creating tobacco-free public places, etc.³⁴
• Early detection of pulmonary fibrosis in smokers–  smoking is a suspected risk factor for the development of pulmonary fibrosis. It is important to have national programmes for early detection in heavy smokers, especially in those at high risk for the development of PF.³⁵ 

Summary

Pulmonary fibrosis is a socially significant disease. There is a clear relationship between smoking and the development and progression of PF. Thus, smoking prevention and smoking cessation programmes should be implemented on a large scale to reduce the burden of this essential disease. Each patient-smoker with PF should be assessed by their healthcare provider at an individual level to decide on the most appropriate method for smoking cessation.