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] However, in most cases the cause is unknown, and termed idiopathic pulmonary fibrosis. [1] [3] Diagnosis may be based on symptoms, medical imaging, lung biopsy, and lung function tests. [1]

No cure exists and only limited treatment options are available. [1] Treatment is directed towards efforts to improve symptoms and may include oxygen therapy and pulmonary rehabilitation. [1] [4] Certain medications may be used to try to slow the worsening of scarring. [4] Lung transplantation may occasionally 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 or may not be abnormal, but high-resolution CT will frequently demonstrate 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 infection like tuberculosis which may cause fibrotic changes in both lung's upper or lower lobes and other microscopic injuries to the lung. However, pulmonary fibrosis can also appear without any known cause. In this 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, there is a growing body of evidence which points to a genetic predisposition in a subset of patients. For example, a mutation in surfactant protein C (SP-C) has been found to exist 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 percent 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] .

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 to send for evaluation. The removed tissue is examined histopathologically by microscopy to confirm the presence and pattern of fibrosis as well as presence of other features that may indicate a specific cause e.g. 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 overall pulmonary fibrosis is not rare, each individual type of pulmonary fibrosis is uncommon and the 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 with the classification of some cases. [26]

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. [27]

Treatment

Pulmonary fibrosis creates scar tissue. The scarring is permanent once it has developed. [28] Slowing the progression and prevention depends on the underlying cause:

The immune system is felt to play a central role in the development of many forms of pulmonary fibrosis. The goal of treatment with immune suppressive agents such as corticosteroids is to decrease lung inflammation and subsequent scarring. Responses to treatment are variable. Those whose conditions improve with immune suppressive treatment probably do not have idiopathic pulmonary fibrosis, for idiopathic pulmonary fibrosis has no significant treatment or cure. [29]

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 with oxygen supplementation. [3]

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

Epidemiology

Globally, the prevalence and incidence of pulmonary fibrosis is studied from the United States, Norway, Czech Republic, Greece, United Kingdom, Finland, and Turkey, with only two studies from Japan, and Taiwan. The issues associated with tracking the epidemiology of pulmonary fibrosis are due to the majority of these studies having participants were diagnosed with pulmonary fibrosis prior to this study. This lowers the diagnosis sensitivity, so with that on mind the has ranged from 0.7 per 100,000 in Taiwan to 63.0 per 100,000 in the United States, and the published incidence has ranged from 0.6 per 100,000 person years to 17.4 per 100,000 person years. [33]

The mean age of all pulmonary fibrosis patients is between 65-70 years old, making age a criterion of its own. The rarity of a person under 50 being diagnosed is because of an aging respiratory system being much more vulnerable to fibrosis and stem cell depletion.

[34] [ needs update ]

Incidence ratePrevalence ratePopulationYears coveredReference
6.8–16.314.0–42.7U.S. health care claims processing system1996–2000Raghu et al. [35]
8.8–17.427.9–63.0Olmsted County, Minnesota1997–2005Fernandez Perez et al. [36]
27.530.3Males in Bernalillo County, New Mexico1988–1990Coultas et al. [37]
11.514.5Females

Based on these rates, pulmonary fibrosis prevalence in the United States 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 numbers 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 the age of fifty. However, loss of pulmonary function is commonly ascribed to old age, heart disease or to more common lung diseases. [38]

Following the COVID-19 pandemic, the rise in deaths for 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 proving long-term impairment of lung function and radiographic abnormalities suggestive of pulmonary fibrosis for patients with lung co-morbidities. [39]

The most common, and long-term consequence in COVID-19 patients, is pulmonary fibrosis. The biggest concerns regarding pulmonary fibrosis and the increase of respiratory follow-up following COVID-19 are supposed to be solved in the near future. Along with the respiratory follow up increases, older age with decreased lung function and/or preexisting co-morbidities, such as diabetes, cardiovascular disease, hypertension, and obesity, increase the risk of later developing fibrotic lung alterations in the COVID-19 survivors with lower exercise tolerance. Following the patients of this study determined that 40% of patients will develop a form of fibrosis of the lungs following COVID-19, and 20% of those patients will be severe instances. [40]

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> Group of diseases

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.

<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">Pneumonitis</span> General inflammation of lung tissue

Pneumonitis describes general inflammation of lung tissue. Possible causative agents include radiation therapy of the chest, exposure to medications used during chemo-therapy, the inhalation of debris, aspiration, herbicides or fluorocarbons and some systemic diseases. If unresolved, continued inflammation can result in irreparable damage such as pulmonary fibrosis.

<span class="mw-page-title-main">Cryptogenic organizing pneumonia</span> Medical condition

Cryptogenic organizing pneumonia (COP), formerly known as bronchiolitis obliterans organizing pneumonia (BOOP), is an inflammation of the bronchioles (bronchiolitis) and surrounding tissue in the lungs. It is a form of idiopathic interstitial pneumonia.

<span class="mw-page-title-main">Respiratory disease</span> Disease of the respiratory system

Respiratory diseases, or lung diseases, are pathological conditions affecting the organs and tissues that make gas exchange difficult in air-breathing animals. They include conditions of the respiratory tract including the trachea, bronchi, bronchioles, alveoli, pleurae, pleural cavity, the nerves and muscles of respiration. Respiratory diseases range from mild and self-limiting, such as the common cold, influenza, and pharyngitis to life-threatening diseases such as bacterial pneumonia, pulmonary embolism, tuberculosis, acute asthma, lung cancer, and severe acute respiratory syndromes, such as COVID-19. Respiratory diseases can be classified in many different ways, including by the organ or tissue involved, by the type and pattern of associated signs and symptoms, or by the cause of the disease.

<span class="mw-page-title-main">Idiopathic pulmonary fibrosis</span> Medical condition

Idiopathic pulmonary fibrosis (IPF), or (formerly) 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 scarring lung disease characterized by a progressive and irreversible decline in lung function. The tissue in the lungs becomes thick and stiff, which affects the tissue that surrounds the air sacs in the lungs. Symptoms typically include gradual onset of shortness of breath and a dry cough. Other changes may include feeling tired, and abnormally large and dome shaped finger and toenails. Complications may include pulmonary hypertension, heart failure, pneumonia or pulmonary embolism.

<span class="mw-page-title-main">Usual interstitial pneumonia</span> Medical condition

Usual interstitial pneumonia (UIP) is a form of lung disease characterized by progressive scarring of both lungs. The scarring (fibrosis) involves the pulmonary interstitium. UIP is thus classified as a form of interstitial lung disease.

<span class="mw-page-title-main">High-resolution computed tomography</span> Diagnostic imaging test

High-resolution computed tomography (HRCT) is a type of computed tomography (CT) with specific techniques to enhance image resolution. It is used in the diagnosis of various health problems, though most commonly for lung disease, by assessing the lung parenchyma. On the other hand, HRCT of the temporal bone is used to diagnose various middle ear diseases such as otitis media, cholesteatoma, and evaluations after ear operations.

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.

Non-specific interstitial pneumonia (NSIP) is a form of idiopathic interstitial pneumonia.

<span class="mw-page-title-main">Scleroderma</span> Group of autoimmune diseases resulting in abnormal growth of connective tissue

Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure. One form of the condition, known as CREST syndrome, classically results in calcium deposits, Raynaud's syndrome, esophageal problems, thickening of the skin of the fingers and toes, and areas of small, dilated blood vessels.

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

Nintedanib, sold under the brand names Ofev and Vargatef, is an oral medication used for the treatment of idiopathic pulmonary fibrosis and along with other medications for some types of non-small-cell lung cancer.

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

Ground-glass opacity (GGO) is a finding seen on chest x-ray (radiograph) or computed tomography (CT) imaging of the lungs. It is typically defined as an area of hazy opacification (x-ray) or increased attenuation (CT) due to air displacement by fluid, airway collapse, fibrosis, or a neoplastic process. When a substance other than air fills an area of the lung it increases that area's density. On both x-ray and CT, this appears more grey or hazy as opposed to the normally dark-appearing lungs. Although it can sometimes be seen in normal lungs, common pathologic causes include infections, interstitial lung disease, and pulmonary edema.

Liver regeneration is the process by which the liver is able to replace lost liver tissue. The liver is the only visceral organ with the capacity to regenerate. The liver can regenerate after partial surgical removal or chemical injury. As little as 51% of the original liver mass is required for the organ to regenerate back to full size. The process of regeneration in mammals is mainly compensatory growth because while the lost mass of the liver is replaced, it does not regain its original shape. During compensatory hyperplasia, the remaining liver tissue becomes larger so that the organ can continue to function. In lower species such as fish, the liver can regain both its original size and mass.

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

Emphysema is any air-filled enlargement in the body's tissues. Most commonly emphysema refers to the enlargement of air spaces (alveoli) in the lungs, and is also known as pulmonary emphysema.

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