The Other Lung Diseases

TL;DR. Asthma and COPD are the lung diseases everyone has heard of. This chapter covers the rest, and several of them are worse. Idiopathic pulmonary fibrosis scars the lungs progressively and has a median survival from diagnosis of three to five years, which is worse than several common cancers. Occupational lung disease was supposed to be a historical problem and is not: silicosis is currently resurging in young workers cutting engineered stone kitchen worktops, and coal workers' pneumoconiosis has returned in the United States. Asbestos continues to kill tens of thousands of people a year from exposures that happened decades ago. And bronchiectasis, permanently widened airways full of infected mucus, is far more common than its low profile suggests. The theme of this chapter is that lungs do not regenerate, so almost everything here is about preventing exposure and slowing decline.

Key takeaways

• Idiopathic pulmonary fibrosis has a median survival of about 3 to 5 years from diagnosis untreated, and two antifibrotic drugs slow the decline without stopping it.
• Silicosis is resurging because of engineered stone worktops, which contain far more crystalline silica than natural stone. Australia became the first country to ban engineered stone in 2024.
• Asbestos-related disease has a latency of 20 to 50 years, so deaths today reflect exposures from the 1960s to 1980s, and countries still using asbestos are creating tomorrow's cases.
• Hypersensitivity pneumonitis is often curable by removing one exposure, most commonly birds or mould, which makes taking a detailed home and hobby history genuinely therapeutic.
• Bronchiectasis is managed largely by physiotherapy, and airway clearance matters more than any drug.
• A tall thin young man with sudden chest pain and breathlessness has a pneumothorax until proven otherwise, and a tension pneumothorax is treated before imaging.

Interstitial lung disease

In short: Over 200 conditions that scar or inflame the tissue between the air sacs, stiffening the lung and blocking oxygen transfer.

What it is

The interstitium is the thin scaffolding between the alveoli and the capillaries, the layer across which oxygen must cross (Chapter 4). Interstitial lung disease (ILD) is a family of over 200 conditions that thicken, inflame, or scar it.

The consequences follow directly from the physics:

• Oxygen cannot cross a thickened barrier easily, so oxygen levels fall, characteristically on exertion first and at rest only later.
• A scarred lung is stiff, so breathing requires more work, producing a rapid shallow breathing pattern.
• Lung volumes shrink, giving a restrictive pattern on breathing tests, the opposite of the obstructive pattern of asthma and COPD.

The shared clinical picture: progressive breathlessness on exertion, a persistent dry cough, fine crackles at the lung bases on listening (often described as sounding like Velcro being pulled apart), reduced oxygen saturation on walking, and, in some, finger clubbing.

The main causes

Distinguishing them matters enormously, because some are treated with immunosuppression and some are made worse by it. This is why diagnosis is made by a multidisciplinary team combining respiratory physicians, thoracic radiologists, and pathologists, which measurably improves diagnostic accuracy.

Idiopathic pulmonary fibrosis

In short: Progressive scarring of unknown cause with a survival worse than several cancers, and two drugs that slow it.

What it is. Progressive fibrosis with a characteristic pattern called usual interstitial pneumonia (UIP) on high-resolution CT: honeycombing and traction bronchiectasis, worst at the lung bases and at the periphery.

Who gets it: typically over 60, more men than women, and strongly associated with smoking. Roughly 3 million people worldwide.

Genetics matter more than the "idiopathic" label suggests. A common variant in the promoter of the MUC5B gene, present in around 20 percent of people of European ancestry, is the strongest known risk factor, increasing risk several-fold. Mutations in telomere maintenance genes cause familial pulmonary fibrosis, connecting the disease to the cellular ageing mechanisms of Chapter 3, and short telomeres predict worse outcomes and poorer tolerance of immunosuppression.

What actually goes wrong. The current model is not primarily inflammatory. Repeated microinjury to ageing alveolar epithelial cells, plausibly from smoking, reflux and micro-aspiration, or inhaled particles, triggers an aberrant wound-healing response. Fibroblasts proliferate, deposit collagen, and do not switch off. The result is progressive replacement of gas-exchange tissue with scar.

That model has a treatment consequence. IPF was treated for decades with steroids and immunosuppression on the assumption it was inflammatory. The PANTHER trial tested that combination formally and found increased death and hospitalisation in the treated arm, and was stopped early. It is a clear demonstration that a plausible mechanism is not a substitute for a trial.

Prognosis: median survival roughly 3 to 5 years from diagnosis without treatment, though the course is variable and unpredictable. Acute exacerbations, sudden unexplained deteriorations over days, carry very high mortality and are a common terminal event.

Treatment:

The concept of progressive pulmonary fibrosis now extends beyond IPF: fibrotic ILD of other causes that continues to worsen despite treatment behaves similarly and responds to nintedanib, which has widened who can be treated.

Hypersensitivity pneumonitis

In short: An allergic reaction in the lung tissue to something inhaled, and removing the exposure can cure it.

What it is. An immune reaction to an inhaled organic antigen, causing inflammation of the alveoli and small airways, which can progress to fibrosis if exposure continues.

The classic exposures, and taking this history is the whole diagnosis:

Presentation is either acute (fever, cough, and breathlessness four to eight hours after exposure, resolving over days, which is why it is often mistaken for recurrent flu or chest infection) or chronic (insidious breathlessness and cough, indistinguishable clinically from other ILD, and progressing to fibrosis).

Treatment is antigen avoidance, which is often curative in non-fibrotic disease and always necessary. Corticosteroids speed recovery, and immunosuppression is used in fibrotic disease. In up to half of cases no antigen is ever identified despite thorough investigation, which is frustrating and carries a worse prognosis.

The practical point: a person with unexplained breathlessness should be asked in detail about birds, damp, hobbies, and work. It is one of the few situations where a history alone can lead to a cure.

Occupational lung disease

In short: Not a historical problem. Silicosis is resurging in young workers, coal workers' lung has returned, and asbestos deaths are still rising in some countries.

Asbestos

Asbestos fibres are thin, sharp, and biopersistent: inhaled, they lodge in the lung and pleura and remain for decades, provoking continuous inflammation and DNA damage.

The timeline is the tragedy. Because of the latency, deaths today reflect exposure from the 1960s to 1980s. Countries that banned asbestos decades ago have only recently passed their peak. Countries still mining and using it, including several large economies, are generating cases that will appear in the 2050s and 2060s. Asbestos remains legal in a substantial part of the world.

Anyone who worked in construction, shipbuilding, insulation, boiler maintenance, or demolition before the bans is potentially exposed, as are people who washed those workers' clothes, which is a documented route to mesothelioma in spouses.

Silicosis, and why it is back

Crystalline silica is in sandstone, granite, concrete, and brick. Cutting, grinding, or drilling them releases respirable particles that cause progressive nodular fibrosis of the lung. It is one of the oldest recognised occupational diseases.

The current resurgence is caused by engineered stone worktops. Natural granite is roughly 30 percent silica; engineered stone can be over 90 percent. Cutting and polishing it, especially dry, produces extremely high silica exposures, and outbreaks of accelerated silicosis in young workers have been reported in Australia, Israel, Spain, the United States, and elsewhere, sometimes in people in their twenties and thirties, some requiring lung transplantation.

Australia banned the manufacture, supply, and installation of engineered stone in 2024, the first country to do so, on the recommendation of its work health and safety regulator.

Silicosis also substantially increases the risk of tuberculosis (Chapter 29), which is why silica-exposed workers in high-TB-burden countries, particularly South African miners, carry a very heavy combined burden. Silica exposure is also linked to lung cancer, kidney disease, and autoimmune disease.

There is no treatment. Prevention is wet cutting, local exhaust ventilation, enclosure, and respiratory protection, with regulation and enforcement doing the actual work.

Coal workers' pneumoconiosis

"Black lung", caused by inhaled coal dust, was expected to disappear with modern controls. It has returned in the United States, particularly in central Appalachia, with rising rates of the severe form, progressive massive fibrosis, in relatively young miners. The leading explanations are thinner remaining coal seams requiring cutting through more silica-containing rock, longer shifts, and inadequate dust control.

Occupational asthma

Roughly 10 to 15 percent of adult-onset asthma is caused by workplace exposure (Chapter 45). It is important because removing the exposure early can cure it, while continued exposure makes it permanent. The characteristic history is symptoms that improve at weekends and on holiday and return at work. Common causes: isocyanates (spray painting), flour (bakers), latex, wood dust, laboratory animals, and hairdressing chemicals.

Bronchiectasis

In short: Permanently widened, damaged airways that fill with infected mucus, in a self-perpetuating cycle broken mainly by physiotherapy.

What it is. Irreversible dilation of the bronchi with destruction of their walls and elastic tissue, so they cannot clear mucus.

The vicious cycle explains the whole disease: impaired clearance leads to bacterial colonisation, which drives inflammation, which damages the airway further, which impairs clearance more.

Causes: post-infective (childhood pneumonia, whooping cough, measles, and, worldwide, prior tuberculosis, which is a major cause), cystic fibrosis (Chapter 57), primary ciliary dyskinesia, immunodeficiency (which should be tested for, since it is treatable), allergic bronchopulmonary aspergillosis, rheumatoid arthritis and inflammatory bowel disease, and aspiration. In a substantial proportion no cause is found.

Symptoms: chronic cough productive of large volumes of sputum, recurrent chest infections, breathlessness, sometimes coughing blood. Diagnosis is by CT.

Treatment, and the order matters:

1. Airway clearance physiotherapy, daily and lifelong. This is the foundation, and it is the part most often under-taught. Techniques include active cycle of breathing, oscillating positive-pressure devices, and postural drainage.
2. Treating exacerbations with prolonged antibiotic courses, guided by sputum culture.
3. Long-term azithromycin in frequent exacerbators, which reduces exacerbations at the cost of resistance selection and hearing monitoring.
4. Inhaled antibiotics for chronic Pseudomonas colonisation.
5. Treating the underlying cause where one is found, particularly immunodeficiency, which is the reason to look.
6. Pulmonary rehabilitation and vaccination.

Pulmonary hypertension

In short: Raised pressure in the lung circulation, which eventually fails the right side of the heart, and only one of its five causes has specific drug treatment.

What it is. Mean pulmonary artery pressure above 20 mmHg. The right ventricle, a thin-walled chamber built to pump against low resistance, must work against a high one, and eventually fails.

Five groups, and the classification determines everything:

Symptoms are non-specific and that is why diagnosis is late: breathlessness on exertion, fatigue, chest pain, fainting on exertion, and eventually leg swelling and abdominal distension from right heart failure. Average delay from symptom onset to diagnosis in PAH remains over two years.

Treatment of group 1 PAH uses three pathways, increasingly in combination from the outset: endothelin receptor antagonists (bosentan, ambrisentan, macitentan), PDE5 inhibitors and guanylate cyclase stimulators (sildenafil, tadalafil, riociguat), and prostacyclin analogues (epoprostenol, treprostinil, selexipag). These transformed a disease with a median survival of under three years in the 1980s into one where many patients live for a decade or more. Sotatercept, a newer agent targeting a different signalling pathway, has recently shown substantial benefit and represents the first genuinely new mechanism in years.

Giving PAH drugs to patients with group 2 or 3 disease can cause harm, which is why the classification is not academic.

Pleural disease

In short: Fluid or air in the space around the lung, and one form is treated before it is imaged.

Pleural effusion is fluid in the pleural space, causing breathlessness and a dull-sounding chest. The first question is whether it is a transudate (from pressure and protein imbalance: heart failure, cirrhosis, kidney disease) or an exudate (from inflammation or malignancy: infection, cancer, pulmonary embolism, autoimmune disease), which is decided by comparing protein and enzyme levels between fluid and blood using Light's criteria. An infected effusion (empyema) requires drainage, because antibiotics do not sterilise a collection of pus.

Pneumothorax is air in the pleural space, causing the lung to collapse.

Don't be confused: a tension pneumothorax is diagnosed clinically and treated immediately, without waiting for an X-ray. Air enters the pleural space with each breath and cannot escape, so pressure rises, compresses the heart and great vessels, and blood cannot return to the heart. The signs are severe respiratory distress, low blood pressure, absent breath sounds on one side, and the trachea pushed away from that side. Treatment is immediate needle decompression followed by a chest drain. Sending this patient to radiology can kill them.

What the person can do

In short: Control exposures, take clearance physiotherapy seriously, and get unexplained breathlessness investigated rather than attributed to age.

• Get progressive breathlessness investigated. Being breathless on stairs is not a normal part of getting older, and interstitial disease, pulmonary hypertension, and bronchiectasis are all routinely attributed to age or weight for years.
• Give a full exposure history: every job, every hobby, birds, damp, hot tubs, and what you did before the job you have now. It changes the diagnosis in a meaningful proportion of ILD.
• If you work with stone, concrete, or brick: wet cutting, extraction, and proper respiratory protection, every time. Dry cutting engineered stone is among the most dangerous common occupational exposures currently happening.
• If you were exposed to asbestos, tell any doctor investigating a chest problem, do not smoke, and know that the latency means decades-old exposure remains relevant.
• If work makes your asthma worse and holidays make it better, report it and get it investigated early, because occupational asthma caught early can be cured and caught late cannot.
• In bronchiectasis, do the airway clearance every day. It works better than most of the drugs and it is the part people quietly abandon.
• Get vaccinated against influenza, pneumococcus, COVID-19, and RSV where offered. In damaged lungs an ordinary infection is not ordinary.
• Sudden sharp one-sided chest pain with breathlessness in a young, tall, thin person should prompt urgent assessment for pneumothorax.

Sources and notes

ILD classification and multidisciplinary diagnosis: ATS/ERS statements. IPF epidemiology, survival, and MUC5B: Raghu et al., ATS/ERS/JRS/ALAT guidelines; Seibold et al., NEJM, 2011 (MUC5B); telomere biology in familial fibrosis: Armanios et al. PANTHER-IPF: NEJM, 2012 (increased mortality with prednisone, azathioprine, and N-acetylcysteine). Pirfenidone: ASCEND, NEJM, 2014. Nintedanib: INPULSIS, NEJM, 2014, and INBUILD for progressive fibrosing ILD, NEJM, 2019. Hypersensitivity pneumonitis: ATS/JRS/ALAT clinical practice guideline, 2020. Asbestos-related disease and mesothelioma latency and epidemiology: WHO and IARC. Engineered stone silicosis outbreaks: Hoy et al., Occupational and Environmental Medicine, and Australian Safe Work recommendations leading to the 2024 prohibition. Resurgent coal workers' pneumoconiosis: Blackley et al., American Journal of Public Health, 2018. Occupational asthma proportion of adult-onset asthma: Toren and Blanc, BMC Pulmonary Medicine, 2009. Bronchiectasis management: ERS and BTS guidelines. Pulmonary hypertension classification and haemodynamic definition: ESC/ERS 2022 guidelines. Sotatercept: STELLAR trial, NEJM, 2023. Light's criteria: Light et al., Annals of Internal Medicine, 1972.

Open questions. What triggers idiopathic pulmonary fibrosis is unknown, and whether the MUC5B variant is causal or a marker remains debated. Whether antifibrotics started earlier, or in people with subclinical interstitial abnormalities on scans done for other reasons, would change outcomes is untested.

Next: the immune system attacking things that were never a threat. 👉