Pulmonary fibrosis

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Pulmonary fibrosis
Other namesInterstitial pulmonary fibrosis
End-stage interstitial lung disease (honeycomb lung).jpg
Lung with end-stage pulmonary fibrosis at autopsy
Clubbing of fingers in IPF.jpg
Clubbing of the fingers in pulmonary fibrosis
Specialty Pulmonology
Symptoms Shortness of breath, dry cough, feeling tired, weight loss, nail clubbing [1]
Complications Pulmonary hypertension, respiratory failure, pneumothorax, lung cancer [2]
Causes Tobacco smoking, environmental pollution, certain medications, connective tissue diseases, interstitial lung disease, unknown [1] [3]
Treatment Oxygen therapy, pulmonary rehabilitation, lung transplantation [4]
Medication Pirfenidone, nintedanib [4]
Prognosis Poor [3]
Frequency>5 million people [5]

Pulmonary fibrosis is a condition in which the lungs become scarred over time. [1] Symptoms include shortness of breath, a dry cough, feeling tired, weight loss, and nail clubbing. [1] Complications may include pulmonary hypertension, respiratory failure, pneumothorax, and lung cancer. [2]

Contents

Causes include environmental pollution, certain medications, connective tissue diseases, infections, and interstitial lung diseases. [1] [3] [6] But in most cases the cause is unknown (idiopathic pulmonary fibrosis). [1] [3] Diagnosis may be based on symptoms, medical imaging, lung biopsy, and lung function tests. [1]

No cure exists and treatment options are limited. [1] Treatment is directed toward improving symptoms and may include oxygen therapy and pulmonary rehabilitation. [1] [4] Certain medications may slow the scarring. [4] Lung transplantation may be an option. [3] At least 5 million people are affected globally. [5] Life expectancy is generally less than five years. [3]

Signs and symptoms

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Lung sound in idiopathic pulmonary fibrosis
velcro crackles on auscultation in a person with idiopathic pulmonary fibrosis
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Symptoms of pulmonary fibrosis are mainly: [1]

Pulmonary fibrosis is suggested by a history of progressive shortness of breath (dyspnea) with exertion. Sometimes fine inspiratory crackles can be heard at the lung bases on auscultation. A chest X-ray may not be abnormal, but high-resolution CT will often show abnormalities. [3]

Cause

Pulmonary fibrosis may be a secondary effect of other diseases. Most of these are classified as interstitial lung diseases. Examples include autoimmune disorders, viral infections, and bacterial infections such as tuberculosis that may cause fibrotic changes in the lungs' upper or lower lobes and other microscopic lung injuries. But pulmonary fibrosis can also appear without any known cause. In that case, it is termed "idiopathic". [7] Most idiopathic cases are diagnosed as idiopathic pulmonary fibrosis . This is a diagnosis of exclusion of a characteristic set of histologic/pathologic features known as usual interstitial pneumonia (UIP). In either case, a growing body of evidence points to a genetic predisposition in a subset of patients. For example, a mutation in surfactant protein C (SP-C) has been found in some families with a history of pulmonary fibrosis. [8] Autosomal dominant mutations in the TERC or TERT genes, which encode telomerase, have been identified in about 15% of pulmonary fibrosis patients. [9]

Diseases and conditions that may cause pulmonary fibrosis as a secondary effect include: [3] [8]

Pathogenesis

Pulmonary fibrosis involves a gradual replacement of normal lung tissue with fibrotic tissue. Such scar tissue causes an irreversible decrease in oxygen diffusion capacity, and the resulting stiffness or decreased compliance makes pulmonary fibrosis a restrictive lung disease. [14] Pulmonary fibrosis is perpetuated by aberrant wound healing, rather than chronic inflammation. [15] It is the main cause of restrictive lung disease that is intrinsic to the lung parenchyma. In contrast, quadriplegia [16] and kyphosis [17] are examples of causes of restrictive lung disease that do not necessarily involve pulmonary fibrosis.

Common genes implicated in fibrosis are Transforming Growth Factor-Beta (TGF-β), [18] Connective Tissue Growth Factor (CTGF), [19] Epidermal Growth Factor Receptor (EGFR), [20] Interleukin-13 (IL-13), [21] Platelet-Derived Growth Factor (PDGF), [22] Wnt/β-catenin signaling pathway, [23] and TNIK. [24] Additionally, chromatin remodeler proteins affect the development of lung fibrosis, as they are crucial for gene expression regulation and their dysregulation can contribute to fibrotic disease progression. [25]

Diagnosis

HRCT of lung showing extensive fibrosis possibly from usual interstitial pneumonitis. There is also a large bulla. Pulmon fibrosis.PNG
HRCT of lung showing extensive fibrosis possibly from usual interstitial pneumonitis. There is also a large bulla.

The diagnosis can be confirmed by lung biopsy. [3] A video-assisted thoracoscopic surgery (VATS) under general anesthesia may be needed to obtain enough tissue to make an accurate diagnosis. This kind of biopsy involves placement of several tubes through the chest wall, one of which is used to cut off a piece of lung for evaluation. The removed tissue is examined histopathologically by microscopy to confirm the presence and pattern of fibrosis as well as other features that may indicate a specific cause, such as specific types of mineral dust or possible response to therapy, e.g. a pattern of so-called non-specific interstitial fibrosis.

Misdiagnosis is common because, while pulmonary fibrosis is not rare, each type is uncommon and evaluation of patients with these diseases is complex and requires a multidisciplinary approach. Terminology has been standardized but difficulties still exist in their application. Even experts may disagree on the classification of some cases. [27]

On spirometry, as a restrictive lung disease, both the FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) are reduced so the FEV1/FVC ratio is normal or even increased, in contrast to obstructive lung disease, where this ratio is reduced. The values for residual volume and total lung capacity are generally decreased in restrictive lung disease. [28]

Treatment

Pulmonary fibrosis creates scar tissue. The scarring is permanent once it has developed. [29] Slowing the progression and prevention depends on the underlying cause:

The immune system is thought to play a central role in the development of many forms of pulmonary fibrosis. The goal of treatment with immunosuppressive agents such as corticosteroids is to decrease lung inflammation and subsequent scarring. Responses to treatment vary. Those whose conditions improve with immunosuppressive treatment probably do not have idiopathic pulmonary fibrosis, for idiopathic pulmonary fibrosis has no significant treatment or cure. [30]

Prognosis

Hypoxia caused by pulmonary fibrosis can lead to pulmonary hypertension, which in turn can lead to heart failure of the right ventricle. Hypoxia can be prevented by oxygen supplementation. [3]

Pulmonary fibrosis may also result in an increased risk of pulmonary emboli, which can be prevented by anticoagulants. [3]

Epidemiology

Globally, the prevalence and incidence of pulmonary fibrosis has been studied in the United States, Norway, Czech Republic, Greece, United Kingdom, Finland, and Turkey, with only two studies in Japan and Taiwan. But most of these studies were of people already diagnosed with pulmonary fibrosis, which lowers the diagnosis sensitivity, so that the prevalence and incidence has ranged from 0.7 per 100,000 in Taiwan to 63.0 per 100,000 in the U.S., and the published incidence has ranged from 0.6 per 100,000 person years to 17.4 per 100,000 person years. [34]

The mean age of all pulmonary fibrosis patients is between 65 and 70 years, making age a criterion of its own. Aging respiratory systems are much more vulnerable to fibrosis and stem cell depletion.

[35] [ needs update ]

Incidence ratePrevalence ratePopulationYears coveredReference
6.8–16.314.0–42.7U.S. health care claims processing system1996–2000Raghu et al. [36]
8.8–17.427.9–63.0Olmsted County, Minnesota1997–2005Fernandez Perez et al. [37]
27.530.3Males in Bernalillo County, New Mexico1988–1990Coultas et al. [38]
11.514.5Females

Based on these rates, pulmonary fibrosis prevalence in the U.S. could range from more than 29,000 to almost 132,000, based on the population in 2000 that was 18 years or older. The actual number may be significantly higher due to misdiagnosis. Typically, patients are in their forties and fifties when diagnosed, while the incidence of idiopathic pulmonary fibrosis increases dramatically after age 50. But loss of pulmonary function is commonly ascribed to old age, heart disease, or more common lung diseases. [39]

Since the COVID-19 pandemic, deaths of people with pulmonary fibrosis increased due to the rapid loss of pulmonary function. The consequences of COVID-19 include a large cohort of patients with both fibrosis and progressive lung impairment. Long-term follow-up studies are showing long-term impairment of lung function and radiographic abnormalities suggestive of pulmonary fibrosis for patients with lung comorbidities. [40]

The most common long-term consequence in COVID-19 patients is pulmonary fibrosis. The biggest concerns about pulmonary fibrosis and the increase of respiratory follow-up after COVID-19 are expected to be solved in the near future. Older age with decreased lung function and/or preexisting comorbidities, such as diabetes, cardiovascular disease, hypertension, and obesity increase the risk of developing fibrotic lung alterations in COVID-19 survivors with lower exercise tolerance. According to one study, 40% of COVID-19 patients develop a form of fibrosis of the lungs, and 20% of those are severe. [41]

Related Research Articles

<span class="mw-page-title-main">Asbestosis</span> Pneumoconiosis caused by inhalation and retention of asbestos fibers

Asbestosis is long-term inflammation and scarring of the lungs due to asbestos fibers. Symptoms may include shortness of breath, cough, wheezing, and chest tightness. Complications may include lung cancer, mesothelioma, and pulmonary heart disease.

<span class="mw-page-title-main">Pulmonary hypertension</span> Increased blood pressure in lung arteries

Pulmonary hypertension is a condition of increased blood pressure in the arteries of the lungs. Symptoms include shortness of breath, fainting, tiredness, chest pain, swelling of the legs, and a fast heartbeat. The condition may make it difficult to exercise. Onset is typically gradual. According to the definition at the 6th World Symposium of Pulmonary Hypertension in 2018, a patient is deemed to have pulmonary hypertension if the pulmonary mean arterial pressure is greater than 20mmHg at rest, revised down from a purely arbitrary 25mmHg, and pulmonary vascular resistance (PVR) greater than 3 Wood units.

<span class="mw-page-title-main">Fibrosis</span> Excess connective tissue in healing

Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue.

<span class="mw-page-title-main">Interstitial lung disease</span> Diseases of the space or tissue between the alveoli of the lungs

Interstitial lung disease (ILD), or diffuse parenchymal lung disease (DPLD), is a group of respiratory diseases affecting the interstitium and space around the alveoli of the lungs. It concerns alveolar epithelium, pulmonary capillary endothelium, basement membrane, and perivascular and perilymphatic tissues. It may occur when an injury to the lungs triggers an abnormal healing response. Ordinarily, the body generates just the right amount of tissue to repair damage, but in interstitial lung disease, the repair process is disrupted, and the tissue around the air sacs (alveoli) becomes scarred and thickened. This makes it more difficult for oxygen to pass into the bloodstream. The disease presents itself with the following symptoms: shortness of breath, nonproductive coughing, fatigue, and weight loss, which tend to develop slowly, over several months. The average rate of survival for someone with this disease is between three and five years. The term ILD is used to distinguish these diseases from obstructive airways diseases.

Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. In PMF, the bony aspects of bone marrow are remodeled in a process called osteosclerosis; in addition, fibroblast secrete collagen and reticulin proteins that are collectively referred to as (fibrosis). These two pathological processes compromise the normal function of bone marrow resulting in decreased production of blood cells such as erythrocytes, granulocytes and megakaryocytes, the latter cells responsible for the production of platelets.

<span class="mw-page-title-main">Hypersensitivity pneumonitis</span> Medical condition

Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis (EAA) is a syndrome caused by the repetitive inhalation of antigens from the environment in susceptible or sensitized people. Common antigens include molds, bacteria, bird droppings, bird feathers, agricultural dusts, bioaerosols and chemicals from paints or plastics. People affected by this type of lung inflammation (pneumonitis) are commonly exposed to the antigens by their occupations, hobbies, the environment and animals. The inhaled antigens produce a hypersensitivity immune reaction causing inflammation of the airspaces (alveoli) and small airways (bronchioles) within the lung. Hypersensitivity pneumonitis may eventually lead to interstitial lung disease.

Neuroendocrine hyperplasia is rare and poorly understood lung condition which is characterized by an abnormal growth of pulmonary neuroendocrine cells in the lungs. It is a non-progressive disease of the interstitial tissues of the lungs. Prior to the findings of the hyperplasia of neuroendocrine cells it was known as tachypnea of infancy, as most children outgrow the need for oxygen supplementation within two to seven years. It is characterized by tachypnea, hypoxemia, and retractions. It is typically diagnosed in infants and children younger than one year of age. There is no currently recognized treatment, infants and children are given oxygen supplementation until they outgrow the need; since neuroendocrine cells do not multiply or get larger in size while the lungs continue to grow. This allows the lung disease to have less effect on lung function with age, although they will always have the same amount of neuroendocrine cells as they were born with.

<span class="mw-page-title-main">Cryptogenic organizing pneumonia</span> Inflammation of the bronchioles and surrounding tissue in the lungs

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<span class="mw-page-title-main">Myofibroblast</span> Cell type with functions of both muscular and fibrous connective tissue

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<span class="mw-page-title-main">Idiopathic pulmonary fibrosis</span> Scarring of the lungs for no known reason

Idiopathic pulmonary fibrosis (IPF) synonymous with cryptogenic fibrosing alveolitis is a rare, progressive illness of the respiratory system, characterized by the thickening and stiffening of lung tissue, associated with the formation of scar tissue. It is a type of chronic pulmonary fibrosis characterized by a progressive and irreversible decline in lung function.

<span class="mw-page-title-main">Usual interstitial pneumonia</span> Scarring of the lungs

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Restrictive lung diseases are a category of extrapulmonary, pleural, or parenchymal respiratory diseases that restrict lung expansion, resulting in a decreased lung volume, an increased work of breathing, and inadequate ventilation and/or oxygenation. Pulmonary function test demonstrates a decrease in the forced vital capacity.

<span class="mw-page-title-main">Fibrothorax</span> Medical condition involving fibrosis of the pleural space

Fibrothorax is a medical condition characterised by severe scarring (fibrosis) and fusion of the layers of the pleural space surrounding the lungs resulting in decreased movement of the lung and ribcage. The main symptom of fibrothorax is shortness of breath. There also may be recurrent fluid collections surrounding the lungs. Fibrothorax may occur as a complication of many diseases, including infection of the pleural space known as an empyema or bleeding into the pleural space known as a haemothorax.

Pancreatic stellate cells (PaSCs) are classified as myofibroblast-like cells that are located in exocrine regions of the pancreas. PaSCs are mediated by paracrine and autocrine stimuli and share similarities with the hepatic stellate cell. Pancreatic stellate cell activation and expression of matrix molecules constitute the complex process that induces pancreatic fibrosis. Synthesis, deposition, maturation and remodelling of the fibrous connective tissue can be protective, however when persistent it impedes regular pancreatic function.

<span class="mw-page-title-main">Pirfenidone</span> Chemical compound

Pirfenidone, sold under the brand name Pirespa among others, is a medication used for the treatment of idiopathic pulmonary fibrosis. It works by reducing lung fibrosis through downregulation of the production of growth factors and procollagens I and II.

<span class="mw-page-title-main">Nintedanib</span> Chemical compound

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<span class="mw-page-title-main">Ground-glass opacity</span> Radiologic sign on radiographs and computed tomography scans

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<span class="mw-page-title-main">Emphysema</span> Air-filled enlargement in the bodys tissues

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