Author:
Kai Knudsen
Updated:
17 May, 2025
Idiopathic interstitial pneumonias (IIP) are a group of several interstitial lung diseases. Here, the most common restrictive lung diseases are presented.
Content:
- Lung fibrosis
- IPF – Idiopathic Pulmonary Fibrosis
- Interstitial Pneumonia – UIP/NSIP (Usual Interstitial Pneumonia – UIP)
- Nonspecific Interstitial Pneumonia (NSIP – nonspecific interstitial pneumonia)
- BOOP, COP (Bronchiolitis Obliterans – Organizing Pneumonia)
- Cryptogenic Organizing Pneumonia (COP/BOOP)
- Pneumoconiosis
- Silicosis
- Asbestosis
- Drug-Induced and Radiation-Induced Lung Disease
- Sarcoidosis
- Allergic Alveolitis (Hypersensitivity Pneumonitis)
Lung fibrosis
Idiopathic Interstitial Pneumonias (IIP)
This is a group of several interstitial lung diseases.
IPF – Idiopathic Pulmonary Fibrosis
Previously, the diagnosis of IFA (Idiopathic Fibrosing Alveolitis) was also used. Morphologically, IPF corresponds to UIP (“usual interstitial pneumonia”). Common symptoms include shortness of breath, fatigue, and cough.
Interstitial Pneumonia – UIP/NSIP (Usual Interstitial Pneumonia – UIP)
The etiology is unknown. The disease responds poorly to treatment and has a poor prognosis. These patients usually need to be transplanted, with both lungs replaced. Lung transplantation has a 5-year mortality rate of about 70-75%.
- UIP is also called cryptogenic fibrosing alveolitis
- Histological pattern is called usual interstitial pneumonia
- For the diagnosis of Idiopathic Pulmonary Fibrosis to be established, a specific histological pattern must be demonstrated while other known causes of the pathology must be excluded.
- Other known causes of the pattern: asbestos, collagen vascular diseases, etc.
- Men are more commonly affected than women.
- Two-thirds of patients are older than 60.
- Leads to severe hypoxemia and cyanosis.
Morphology in UIP
- A specific histological pattern called interstitial pneumonia (UIP) is seen.
- Macroscopically, the surface of the lung resembles cobblestones due to scars in the interlobular septa that have contracted.
- The cut surface shows fibrosis (solid rubbery white surfaces).
- The lower lobes dominate in fibrosis.
- Microscopically, patchy interstitial fibrosis is seen, varying in intensity and over time. Many fibroblasts are present initially, then more collagenous scars that are not very cellular. The walls of the alveoli collapse. Cysts form that are lined by type-2 pneumocytes or bronchiolar epithelium (“honeycomb pattern”). Lung arteries often change due to the pulmonary hypertension with hyperplasia, and intima and media thicken.
Clinical Presentation
- Insidious disease course with gradually worsening lung function. The patient develops a dry cough and gradually more shortness of breath.
- Dry or “Velcro-like” inspiratory crackles are common.
- Cyanosis, cor pulmonale, peripheral edema may occur later.
Nonspecific Interstitial Pneumonia (NSIP – nonspecific interstitial pneumonia)
Shortness of breath and cough for several months are the most common symptoms. The diagnosis of NSIP can be established when the patient has pneumonia with interstitial changes without another diagnosis, either cellular or fibrous histopathological pattern. The cellular pattern indicates a better prognosis for the patient than the fibrous one.
- NSIP shows a different histopathological pattern than that of idiopathic pulmonary fibrosis.
- NSIP has a better prognosis than idiopathic pulmonary fibrosis, so it is essential to establish the diagnosis.
Morphology
- Cellular changes with mild to moderate chronic interstitial inflammation with lymphocytes and some plasma cells. A uniform or patchy pattern can be seen.
- Histopathologically, the fibrous changes have a diffuse or patchy interstitial distribution in which all scars are of the same age (unlike idiopathic pulmonary fibrosis, which has scars of different ages).
- Fibroblast foci are often absent.
BOOP, COP (Bronchiolitis Obliterans – Organizing Pneumonia)
Responds better to treatment. Treatment is given with steroids, cortisone. BOOP has a relatively good prognosis.
Cryptogenic Organizing Pneumonia (COP/BOOP)
- Also called Bronchiolitis Obliterans Organizing Pneumonia (BOOP).
- Cryptogenic = unknown etiology.
- Patchy consolidation of the airways is seen. The infiltrates appear the same as in pneumonia but have the peculiarity of moving over time. The symptoms are also the same.
- The disease is often diagnosed in an infectious disease department where a patient with pneumonia does not respond to antibiotics. A new chest X-ray is taken, and the infiltrates are seen to have moved. Treatment is usually given with cortisone, and the patient improves.
- Polyploid plugs of loose connective tissue form in alveolar ducts, alveoli, and bronchioles.
- The connective tissue is the same age everywhere.
- The lung architecture is intact.
- Some patients recover spontaneously, but most require treatment with oral steroids for 6 months or more.
- This disease can also occur as a complication of infections or inflammatory damage to the lung. Then it is no longer “cryptogenic.”
Pneumoconiosis
- Non-cancerous diseases resulting from the inhalation of mineral dust, organic and inorganic particles, and chemical fumes and vapors.
- The most common mineral-induced pneumoconiosis results from the inhalation of coal dust, silica, and asbestos.
- These diseases are almost always work-related and were more common in the past.
Pathogenesis
- Particles are most harmful if they get stuck in the bifurcations of the distal airways.
- Particles > 500 μm are too large to get out.
- Particles < 0.5 μm tend to act like gases and move in and out of the alveoli without depositing and causing significant damage.
- Particles around 1-5 μm are the most dangerous.
- Coal is relatively inert, and large amounts must be deposited in the lungs to cause damage.
- Silica, asbestos, and beryllium are more reactive and lead to fibrotic reactions at lower concentrations.
- Most particles get caught in the cilia and are moved up again by mucus.
- However, some get stuck in bifurcations and attract macrophages that phagocytize them.
- The more reactive particles trigger macrophages to release substances that start an inflammatory response with fibroblast proliferation and collagen deposition.
- Some particles can reach lymph nodes via drainage or inside migrating macrophages and thus start an immune response against components on the particles or self-proteins modified by the particles.
- Leads to amplification and extension of the local reaction.
- Smoking worsens the effects of all inhaled mineral dust. This is particularly true for asbestos.
Coal Worker’s Pneumoconiosis
- Occurs (mainly in the past) in coal miners due to the coal dust they inhale during mining work.
- Affects different patients to varying degrees: asymptomatic anthracosis (coal dust lung): Pigment accumulation without apparent cellular reaction.
- Simple coal worker’s pneumoconiosis: accumulation of macrophages with little or no pulmonary dysfunction.
- Complicated coal worker’s pneumoconiosis: Fibrosis is extensive, and lung function is impaired.
- The patient develops progressive massive fibrosis (PMF).
- Wide range of clinical effects: from asymptomatic pigmentation to mild dysfunction to pulmonary dysfunction, pulmonary hypertension, and cor pulmonale.
- Fibrosis (PMF) tends to worsen without more coal being inhaled.
- Coal mine dust contains a variety of trace metals that can increase the harmful effects of the coal in the dust.
- No increased risk of bronchogenic carcinoma in coal miners compared to the general population, considering smoking as a risk factor. This distinguishes coal exposure from silica and asbestos.
Silicosis
- The most prevalent chronic occupational disease in the world.
- Inhalation of crystalline silica: In the form of quartz, cristobalite, tridymite (quartz is the most common cause of silicosis among these).
- Pathogenesis: The silica particles are eaten by macrophages and activate these due to their reactivity. The macrophages release IL1, TNF, fibronectin, lipid mediators [PG, TX?], free radicals, fibrogenic cytokines [PDGF, TGFβ?].
- Silica is less toxic when mixed with other metals.
- Miners who mine hematite ore can have more silica in their lungs than some sick quartz-exposed workers but still have a relatively mild disease due to the iron in the ore having a protective effect.
- Silicosis is usually detected during routine X-rays on asymptomatic workers exposed to silica dust.
- Fine nodules are found in the upper lungs, but the impact on lung function is usually minimal or none.
- Symptoms appear later when the disease has progressed to PMF. Then patients develop pulmonary hypertension, and cor pulmonale.
- It takes a long time to die from the disease, but work capacity may be significantly reduced due to decreased lung function.
- Silica exposure increases the risk of tuberculosis, probably due to suppression of cell-mediated immunity and making it harder for macrophages to destroy phagocytized bacteria due to the silica crystals they have eaten.
- Silica crystals are carcinogenic.
Asbestosis
- Asbestos exposure causes parenchymal interstitial fibrosis (asbestosis), localized fibrous plaques, or diffuse fibrosis in the pleura, pleural effusions (fluid in the pleura), bronchogenic carcinoma, laryngeal carcinoma, malignant pleural, and peritoneal mesothelioma.
- Whether exposure makes a person sick is determined by asbestos concentration, size, shape, and solubility.
- Serpentine asbestos is curly and flexible. It is more easily trapped in the upper respiratory tract’s mucus and transported out of the lungs. It is also more water-soluble and is washed out of lung tissue if trapped further down.
- Amphibole asbestos is a straight, stiff, and brittle fiber. It is the most pathogenic. The amphibole asbestos particles lay straight in the airflow and pass further down into the airways. They can penetrate the airway epithelium down there and enter the underlying connective tissue.
- Both forms can cause asbestosis and cancer.
- Asbestos causes fibrosis by interacting with lung macrophages.
- Asbestosis causes progressively worsening shortness of breath that occurs 10-20 years after asbestos exposure. Patients usually also develop a productive cough (sputum is coughed up).
- The disease may remain static or progress to heart failure, cor pulmonale, and death.
- Patients have a 5-fold increased risk of bronchogenic carcinoma.
- Cigarette smoking combined with asbestos exposure increases the risk of developing this cancer significantly; smoking + asbestos = 50-fold increased risk of bronchial carcinoma.
- The risk of malignant mesothelioma is increased 1000-fold (this cancer is very rare, 2-17 cases per 1,000,000 ordinary people).
- Pleural plaques: White plaques located on visceral/parietal pleura at the hilum level. They can also be located on the diaphragm. If they contain calcium, they are pathognomonic for asbestosis.
Drug-Induced and Radiation-Induced Lung Disease
- Both acute and chronic damage to the lungs.
- Bleomycin, a cancer drug, can cause pneumonitis and interstitial fibrosis due to the drug’s direct toxicity and the infiltration of inflammatory cells into the alveoli.
- Amiodarone (Cordarone), an antiarrhythmic drug, can also cause interstitial fibrosis and pneumonitis.
- Radiation therapy for lung cancer causes acute pneumonitis after 1-6 months in 20% of all treated patients. It causes fever and shortness of breath disproportionate to the amount of lung irradiated. It may heal with corticosteroid treatment or progress to chronic radiation pneumonitis.
Granulomatous Diseases
Sarcoidosis
- The most common idiopathic interstitial lung disease.
- Sarcoidosis is a multisystem disease with unknown etiology.
- Characterized by non-caseating granuloma formation in many organs and tissues. In the lungs, granulomas form in the parenchyma and mediastinal lymph nodes.
- Mycobacterial and fungal infections can also cause these granulomas, so the diagnosis of sarcoidosis is made only when these have been ruled out.
- Lung involvement often provides the main symptoms leading to the disease’s discovery.
Symptoms
- Acute: Acute sarcoidosis typically presents with bilateral angry ankle arthritis, more often in women. The patient has a fever, low/no CRP, and has had a cough for a while in the history.
- Chronic: Uveitis/iritis. Prolonged cough.
- Skin rash: Seen with skin involvement. Red rash that tends to appear in old scars (e.g., after surgeries), which then change shape. Biopsy shows granulomas. Erythema nodosum.
- Very variable course.
- Entirely asymptomatic in many individuals.
- 2/3 of those who develop symptoms have respiratory symptoms.
- Shortness of breath, dry cough, vague substernal discomfort.
Diagnosis
- Chest X-ray: Shows bilateral hilar lymphomas. Unilateral lymphomas suggest TBC/lymphoma/lung cancer.
- Diagnosis is made when non-caseating granulomas are found in a biopsy, and all other known causes of their occurrence have been excluded.
- Serum-ACE: Indicates disease activity.
Treatment
- Corticosteroids: 40 mg prednisolone in a tapering regimen.
- Methotrexate: Absolute treatment indication is sarcoidosis + uveitis.
Prognosis
- 60-75% of affected individuals recover with minimal or no residual impairment. Those with acute onset have a better prognosis.
- 20% develop permanent lung dysfunction or vision loss. The disease can also affect other organs (CNS, heart).
- 10-15% succumb to progressive pulmonary fibrosis and cor pulmonale.
Allergic Alveolitis (Hypersensitivity Pneumonitis)
- Called allergic alveolitis as it affects the alveoli, unlike asthma, which primarily affects the bronchi.
- Immunologically mediated inflammatory disease: A mixture of type III (immune complex) and type IV (cell-mediated) hypersensitivity.
- Most commonly results from heightened sensitivity to musty hay or other antigens inhaled at the workplace (agriculture).
- The triggering substances are very different, but the syndromes that occur have similar clinical and pathological findings and likely very similar pathophysiology.
- Examples of agents: Bacteria, fungi, animal proteins (pigeon, budgerigar, rats, pigs, cows), chemicals.
- Named after the triggering agent: “Farmer’s lung, Bird breeder’s lung, Sawmill lung.”
- Causes restrictive lung disease with reduced diffusion capacity, compliance, and total lung volume.
Morphology
- Patchy mononuclear infiltrates in the lung interstitium.
- Interstitial non-caseating granulomas (as in sarcoidosis) are seen in 2/3 of cases.
- In advanced chronic cases, diffuse interstitial fibrosis occurs.
Symptoms
- Acute reaction 48 hours after exposure to the antigen: fever (39 degrees), dry cough, shortness of breath, myalgia, arthralgia. If exposure to the antigen is removed after the acute attack, the disease heals completely.
- Chronic disease: If the antigen is not removed from the environment, the patient eventually develops chronic interstitial lung disease (diffuse interstitial changes in the lungs) without the acute severe episodes after exposure. Insidious chronic onset with productive cough, shortness of breath, fatigue, nausea, and weight loss.
Diagnosis
- Crackles and wheezes and possibly cyanosis in acute form.
- Precipitating antibodies against mold panel.
Treatment
- Cortisone in tapering dose in acute disease.
- Remove the agent! If this is done, lung function can fully recover. If fibrosis has occurred, the impairment is permanent. Removing an agent may involve a significant lifestyle change. A farmer may have to stop working on their farm, for example.
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