Emphysema

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Emphysema
Emphysema, centrilobular (4563270814).jpg
Advanced centrilobular emphysema showing total lobule involvement on the left side
Specialty Pulmonology
Symptoms Shortness of breath, chronic cough [1]
Usual onsetOver 40 years old [1]
DurationLong term [1]
Causes Tobacco smoking, air pollution, genetics [1]
Diagnostic method Spirometry [2]
Differential diagnosis Asthma, congestive heart failure, bronchiectasis, tuberculosis, obliterative bronchiolitis, diffuse panbronchiolitis [3]
Prevention Smoking cessation, improving indoor and outdoor air quality, tobacco control measures [4]
Treatment Pulmonary rehabilitation, long-term oxygen therapy, lung volume reduction [4]
Medication Inhaled bronchodilators and corticosteroids [4]

Emphysema is any air-filled enlargement in the body's tissues. [5] Most commonly emphysema refers to the enlargement of air spaces (alveoli) in the lungs, [5] and is also known as pulmonary emphysema.

Contents

Emphysema is a lower respiratory tract disease, [6] characterised by enlarged air-filled spaces in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the alveoli, which replace the spongy lung tissue. This reduces the total alveolar surface available for gas exchange leading to a reduction in oxygen supply for the blood. [7] Emphysema usually affects the middle aged or older population because it takes time to develop with the effects of tobacco smoking, and other risk factors. Alpha-1 antitrypsin deficiency is a genetic risk factor that may lead to the condition presenting earlier. [8]

When associated with significant airflow limitation, emphysema is a major subtype of chronic obstructive pulmonary disease (COPD), a progressive lung disease characterized by long-term breathing problems and poor airflow. [9] [10] Without COPD, the finding of emphysema on a CT lung scan still confers a higher mortality risk in tobacco smokers. [11] In 2016 in the United States there were 6,977 deaths from emphysema – 2.2 per 100,000 of the population. [12] Globally it accounts for 5% of all deaths. [13] A 2018 review of work on the effects of tobacco and cannabis smoking found that a possibly cumulative toxic effect could be a risk factor for developing emphysema, and spontaneous pneumothorax. [14] [15]

There are four types of emphysema, three of which are related to the anatomy of the lobules of the lung – centrilobular or centriacinar, panlobular or panacinar, and paraseptal or distal acinar emphysema – and are not associated with fibrosis (scarring). [16] The fourth type is known as paracicatricial emphysema or irregular emphysema that involves the acinus irregularly and is associated with fibrosis. [16] Though the different types can be seen on imaging they are not well-defined clinically. [17] There are also a number of associated conditions including bullous emphysema, focal emphysema, and Ritalin lung. Only the first two types of emphysema – centrilobular and panlobular – are associated with significant airflow obstruction, with that of centrilobular emphysema around 20 times more common than panlobular. Centrilobular emphysema is the only type associated with smoking. [16]

Osteoporosis is often a comorbidity of emphysema. The use of systemic corticosteroids for treating exacerbations is a significant risk factor for osteoporosis, and their repeated use is recommended against. [18]

Signs and symptoms

Diagram of alveoli with emphysema Blausen 0343 Emphysema.png
Diagram of alveoli with emphysema

Emphysema is a respiratory disease of the lower respiratory tract. [6] It is commonly caused by tobacco smoking but a significant number of people are affected who either do not smoke, or have never smoked. [13] The presence of emphysema is a clear risk factor for the development of lung cancer, made stronger in those who smoke. [19]

Early symptoms of emphysema may vary from person to person. Symptoms can include a cough (with or without sputum), wheezing, a fast breathing rate, breathlessness on exertion, and a feeling of tightness in the chest. There may be frequent cold or flu infections. [1] Other symptoms may include anxiety, depression, fatigue, sleep problems and weight loss. These symptoms could also relate to other lung conditions or other health problems; [20] therefore, emphysema is often underdiagnosed.[ citation needed ] The shortness of breath caused by emphysema can increase over time and develop into chronic obstructive pulmonary disease.

A sign of emphysema in smokers is the finding of a higher number of alveolar macrophages sampled from the bronchoalveolar lavage (BAL) in the lungs. The number can be four to six times greater in those who smoke than in non-smokers. [21]

Emphysema is also associated with barrel chest.

Types

There are four main types of emphysema, three of which are related to the anatomy of the lobules of the lung – centrilobular or centriacinar, panlobular or panacinar, and paraseptal or distal acinar and are not associated with fibrosis (scarring). [16] Although fibrosis is not a normal feature of these subtypes, repair strategies in end-stage emphysema may lead to pulmonary fibrosis. [13] The fourth subtype is known as paracicatricial emphysema or irregular emphysema, involves the acinus irregularly and is associated with fibrosis. [16]

Only the first two types of emphysema – centrilobular and panlobular – are associated with significant airflow obstruction, with that of centrilobular emphysema around 20 times more common than panlobular. [16] The subtypes can be seen on imaging but are not well-defined clinically. [17] There are also a number of associated conditions including bullous emphysema, focal emphysema, and Ritalin lung.

Centrilobular

Stained lung tissue from end-stage emphysema Emphysema H and E.jpg
Stained lung tissue from end-stage emphysema

Centrilobular emphysema, also called centriacinar emphysema, affects the centre of a pulmonary lobule (centrilobular) in the lung, the area around the terminal bronchiole and the first respiratory bronchiole, and can be seen on imaging as an area around the tip of the visible pulmonary artery. Centrilobular emphysema is the most common type usually associated with smoking, and with chronic bronchitis. [16] The disease progresses from the centrilobular portion, leaving the lung parenchyma in the surrounding (perilobular) region preserved. [22] Usually the upper lobes of the lungs are affected. [16]

Panlobular

Panlobular emphysema, also called panacinar emphysema, affects all of the alveoli in a lobule, and can involve the whole lung or mainly the lower lobes. [17] [23] This type of emphysema is associated with alpha-1 antitrypsin deficiency (A1AD or AATD), and Ritalin lung, [23] and is not related to smoking. [17]

Complications

Likely complications of centrilobular and panlobular emphysema, some of which are life-threatening, include: respiratory failure, pneumonia, respiratory infections, pneumothorax, interstitial emphysema, pulmonary heart disease, and respiratory acidosis. [24]

Paraseptal

Paraseptal emphysema, also called distal acinar emphysema, relates to emphysematous change next to a pleural surface, or to a fissure. [17] [25] The cystic spaces known as blebs or bullae that form in paraseptal emphysema typically occur in just one layer beneath the pleura. This distinguishes it from the honeycombing of small cystic spaces seen in fibrosis that typically occurs in layers. [25] This type of emphysema is not associated with airflow obstruction. [26]

Bullous

CT scan of bullous emphysema Bullus emphasemaCT.png
CT scan of bullous emphysema

When the subpleural bullae are significant, the emphysema is called bullous emphysema. Bullae can become extensive and combine to form giant bullae. These can be large enough to take up a third of a hemithorax, compress the lung parenchyma, and cause displacement. The emphysema is now termed giant bullous emphysema, more commonly called vanishing lung syndrome due to the compressed parenchyma. [27] A bleb or bulla may sometimes rupture and cause a pneumothorax. [16]

Paracicatricial

Paracicatricial emphysema, also known as irregular emphysema, is seen next to areas of fibrosis (scarring) as large spaces. The scarring is most often a result of silicosis, granulomatous infection, tuberculosis, or pulmonary infarction. It can be difficult to differentiate from the honeycombing of pulmonary fibrosis. [28]

HIV associated

Classic lung diseases are a complication of HIV/AIDS with emphysema being a source of disease. HIV is cited as a risk factor for the development of emphysema and COPD regardless of smoking status. [29] Around 20 percent of those with HIV have increased emphysematous changes. This has suggested that an underlying mechanism related to HIV is a contributory factor in the development of emphysema. HIV associated emphysema occurs over a much shorter time than that associated with smoking; an earlier presentation is also seen in emphysema caused by alpha-1 antitrypsin deficiency. Both of these conditions predominantly show damage in the lower lungs, which suggests a similarity between the two mechanisms. [30]

Emphysema may develop in some people with alpha-1 antitrypsin deficiency, the only genotype of chronic obstructive pulmonary disease. This usually occurs a lot earlier (as does HIV associated emphysema) than other types. [31]

Ritalin lung

The intravenous use of methylphenidate, commonly marketed as Ritalin and widely used as a stimulant drug in the treatment of attention deficit hyperactivity disorder, can lead to emphysematous changes known as Ritalin lung. The mechanism underlying this link is not clearly understood. Ritalin tablets contain talc as a filler, and need to be crushed and dissolved for injecting. It has been suggested that the talc exposure causes granulomatosis leading to alveolar destruction. However, other intravenous drugs also contain talc, and no emphysematous change is associated with those. High resolution CT scanning shows the emphysema to be panlobular. [32]

CPFE

Combined pulmonary fibrosis and emphysema (CPFE) is a rare syndrome that shows upper-lobe emphysema, together with lower-lobe interstitial fibrosis. This is diagnosed by CT scan. [33] This syndrome presents a marked susceptibility for the development of pulmonary hypertension. [34]

SRIF

Smoking-related interstitial fibrosis (SRIF) is another type of fibrosis that occurs in emphysematous lungs and can be identified by pathologists. Unlike CPFE, this type of fibrosis is usually clinically occult (i.e., does not cause symptoms or imaging abnormalities). Occasionally, however, some patients with SRIF present with symptoms and radiologic findings of interstitial lung disease. [35]

Congenital lobar

Congenital lobar emphysema (CLE), also known as congenital lobar overinflation and infantile lobar emphysema, [36] is a neonatal condition associated with enlarged air spaces in the lungs of newborn infants. It is diagnosed around the time of birth or in the first 6 months of life, occurring more often in boys than girls. CLE affects the upper lung lobes more than the lower lobes, and the left lung more often than the right lung. [37] CLE is defined as the hyperinflation of one or more lobes of the lung due to the partial obstruction of the bronchus. This causes symptoms of pressure on the nearby organs. It is associated with several cardiac abnormalities such as patent ductus arteriosus, atrial septal defect, ventricular septal defect, and tetralogy of Fallot. [38] Although CLE may be caused by the abnormal development of bronchi, or compression of airways by nearby tissues, no cause is identified in half of cases. [37] CT scan of the lungs is useful in assessing the anatomy of the lung lobes and status of the neighbouring lobes on whether they are hypoplastic or not. Contrast-enhanced CT is useful in assessing vascular abnormalities and mediastinal masses. [38]

Focal

A large bulla and a smaller bleb illustrated Pneumot rax bullae.JPG
A large bulla and a smaller bleb illustrated

Focal emphysema is a localized region of emphysema in the lung that is larger than alveoli, and often associated with coalworker's pneumoconiosis. [39] This is also known as localized pulmonary emphysema. [40] Blebs and bullae may also be included as focal emphysema. These can be differentiated from the other type of enclosed air space known as a lung cyst by their size and wall thickness. A bleb or bulla has a wall thickness of less than 1 mm, and are smaller. [41]

Occupational

A number of occupations are associated with the development of emphysema due to the inhalation of varied gases and particles. In the US uranium mining that releases radon gas and particles has been shown to be a cause of emphysema deaths; the figures in the study included some miners who also smoked. Uranium mining and milling was found to create environmental pollution. [42]

The inhalation of coal mine dust that can result in coalworker's pneumoconiosis is an independent risk factor for the development of emphysema. Focal emphysema is associated with the coal macule, and this extends into progressive centrilobular emphysema. Less commonly a variant of panlobular emphysema develops. [43]

Silicosis results from the inhalation of silica particles, and the formation of large silica nodules is associated with paracicatricial emphysema, with or without bullae. [44]

Ozone-induced emphysema

Ozone is another pollutant that can affect the respiratory system. Long-term exposure to ozone can result in emphysema. [45]

Osteoporosis

Osteoporosis is a major comorbidity of emphysema. Both conditions are associated with a low body mass index. [46] There is an association between treating emphysema, and osteoporosis; the use of systemic corticosteroids for treating exacerbations is a significant risk factor for osteoporosis, and their repeated use is not recommended. [18]

Other terms

Compensatory emphysema is overinflation of part of a lung in response to either removal by surgery of another part of the lung or decreased size of another part of the lung. [47]

Pulmonary interstitial emphysema (PIE) is a collection of air inside the lungs but outside the normal air space of the alveoli, found as pneumatoses inside the connective tissue of the peribronchovascular sheaths, interlobular septa, and visceral pleura.

Lung volume reduction

Lung volume reduction may be offered to those with advanced emphysema. When other treatments fail, and the emphysema is located in the upper lobes, a surgical option may be possible. [48] A number of minimally invasive bronchoscopic procedures are increasingly used to reduce lung volume. [49]

Surgical

Where there is severe emphysema with significant hyperinflation that has proved unresponsive to other therapies, lung volume reduction surgery (LVRS) may be an option. [50] [51] LVRS involves the removal of tissue from the lobe most damaged by emphysema, which allows the other lobes to expand and give improved function. The procedure appears to be particularly effective if the emphysema primarily involves the upper lobes; however, the procedure increases the risk of adverse events and early death in people who have diffuse emphysema. [52] [48]

Bronchoscopic

Minimally invasive bronchoscopic procedures may be carried out to reduce lung volume. These include the use of valves, coils, or thermal ablation. [53] [54] Endobronchial valves are one-way valves that may be used in those with severe hyperinflation resulting from advanced emphysema; a suitable target lobe and no collateral ventilation are required for this procedure. The placement of one or more valves in the lobe induces a partial collapse of the lobe that ensures a reduction in residual volume that improves lung function, the capacity for exercise, and quality of life. [55]

The placement of endobronchial coils made of nitinol, instead of valves is recommended where there is collateral ventilation that would prevent the use of valves. [56] [57] Nitinol is a biocompatible shape-memory alloy.

Both of these techniques are associated with adverse effects, including persistent air leaks and cardiovascular complications. Bronchoscopic thermal vapor ablation has an improved profile. Heated water vapor is used to target affected lobe regions, which leads to permanent fibrosis and volume reduction. The procedure is able to target individual lobe segments, can be carried out regardless of collateral ventilation, and can be repeated with the natural advance of emphysema. [58]

Other surgeries

Lung transplantation – the replacement of either a single lung or both (bilateral) – may be considered in end-stage disease. A bilateral transplant is the preferred choice as complications can arise in a remaining single native lung; complications can include hyperinflation, pneumonia, and the development of lung cancer. [59] Careful selection as recommended by the National Emphysema Treatment Trial (NETT) for transplant surgeries is needed as in some cases there will be an increased risk of mortality. [48] Several factors including age, and poor exercise tolerance, using the BODE index need to be taken into account. [59] A transplant is only considered where there are no serious comorbidites. [49] A CT scan or a ventilation/perfusion scan may be useful in surgery considerations to evaluate cases for surgical interventions, and also to evaluate post-surgery responses. [60] A bullectomy may be carried out when a giant bulla occupies more than a third of a hemithorax. [49]

In other tissues

Trapped air can also develop in other tissues such as under the skin, known as subcutaneous emphysema. Orbital emphysema is the trapping of air in the orbit; a type of this is palpebral emphysema that affects just the eyelids. [61] Emphysematous gastritis is the presence of air in the stomach wall, usually caused by a bacterial infection. This is a rare occurrence but has a high mortality rate. [62]

History

Giovanni Battista Morgagni, who recorded one of the earliest descriptions of emphysema in 1769 Giambattista morgagni.gif
Giovanni Battista Morgagni, who recorded one of the earliest descriptions of emphysema in 1769

The terms emphysema and chronic bronchitis were formally defined in 1959 at the CIBA guest symposium, and in 1962 at the American Thoracic Society Committee meeting on Diagnostic Standards. [63] The word emphysema is derived from Ancient Greek ἐμφύσημα 'inflation, swelling' [64] (referring to a lung inflated by air-filled spaces), itself from ἐμφυσάωemphysao 'to blow in, to inflate', [65] composed of ἐν en, meaning "in", and φυσᾶ physa, [66] meaning "wind, blast". [67] [68]

René Laennec, the physician who invented the stethoscope, used the term emphysema in his book A Treatise on the Diseases of the Chest and of Mediate Auscultation (1837) to describe lungs that did not collapse when he opened the chest during an autopsy. [63] He noted that they did not collapse as usual because they were full of air and the airways were filled with mucus. [63] Early descriptions of probable emphysema include: in 1679 by T. Bonet of a condition of "voluminous lungs" and in 1769 by Giovanni Morgagni of lungs which were "turgid particularly from air". [63] [69] In 1721 the first drawings of emphysema were made by Ruysh. [69] These were followed the illustrations of Matthew Baillie in 1789 and descriptions of the destructive nature of the condition.

Related Research Articles

<span class="mw-page-title-main">Lung</span> Primary organ of the respiratory system

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<span class="mw-page-title-main">Bronchus</span> Airway in the respiratory tract

A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi to branch from the trachea at the carina are the right main bronchus and the left main bronchus. These are the widest bronchi, and enter the right lung, and the left lung at each hilum. The main bronchi branch into narrower secondary bronchi or lobar bronchi, and these branch into narrower tertiary bronchi or segmental bronchi. Further divisions of the segmental bronchi are known as 4th order, 5th order, and 6th order segmental bronchi, or grouped together as subsegmental bronchi. The bronchi, when too narrow to be supported by cartilage, are known as bronchioles. No gas exchange takes place in the bronchi.

<span class="mw-page-title-main">Alpha-1 antitrypsin deficiency</span> Medical condition

Alpha-1 antitrypsin deficiency is a genetic disorder that may result in lung disease or liver disease. Onset of lung problems is typically between 20 and 50 years of age. This may result in shortness of breath, wheezing, or an increased risk of lung infections. Complications may include chronic obstructive pulmonary disease (COPD), cirrhosis, neonatal jaundice, or panniculitis.

<span class="mw-page-title-main">Non-invasive ventilation</span> Breathing support administered through a face mask

Non-invasive ventilation (NIV) is the use of breathing support administered through a face mask, nasal mask, or a helmet. Air, usually with added oxygen, is given through the mask under positive pressure; generally the amount of pressure is alternated depending on whether someone is breathing in or out. It is termed "non-invasive" because it is delivered with a mask that is tightly fitted to the face or around the head, but without a need for tracheal intubation. While there are similarities with regard to the interface, NIV is not the same as continuous positive airway pressure (CPAP), which applies a single level of positive airway pressure throughout the whole respiratory cycle; CPAP does not deliver ventilation but is occasionally used in conditions also treated with NIV.

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

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<span class="mw-page-title-main">Acute exacerbation of chronic obstructive pulmonary disease</span> Medical condition

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<span class="mw-page-title-main">Chronic obstructive pulmonary disease</span> Lung disease involving long-term poor airflow

Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease characterized by long-term respiratory symptoms and airflow limitation. The main symptoms of COPD include shortness of breath and a cough, which may or may not produce mucus. COPD progressively worsens, with everyday activities such as walking or dressing becoming difficult. While COPD is incurable, it is preventable and treatable. The two most common types of COPD are emphysema and chronic bronchitis and have been the two classic COPD phenotypes. However, this basic dogma has been challenged as varying degrees of co-existing emphysema, chronic bronchitis, and potentially significant vascular diseases have all been acknowledged in those with COPD, giving rise to the classification of other phenotypes or subtypes. Emphysema is defined as enlarged airspaces (alveoli) whose walls have broken down resulting in permanent damage to the lung tissue. Chronic bronchitis is defined as a productive cough that is present for at least three months each year for two years. Both of these conditions can exist without airflow limitation when they are not classed as COPD. Emphysema is just one of the structural abnormalities that can limit airflow and can exist without airflow limitation in a significant number of people. Chronic bronchitis does not always result in airflow limitation but in young adults with chronic bronchitis who smoke, the risk of developing COPD is high. Many definitions of COPD in the past included emphysema and chronic bronchitis, but these have never been included in GOLD report definitions. Emphysema and chronic bronchitis remain the predominant phenotypes of COPD but there is often overlap between them and a number of other phenotypes have also been described. COPD and asthma may coexist and converge in some individuals. COPD is associated with low-grade systemic inflammation.

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<span class="mw-page-title-main">Pneumatosis</span> Abnormal presence of air or other gas within tissues

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<span class="mw-page-title-main">Focal lung pneumatosis</span> Medical condition

A focal lung pneumatosis, is an enclosed pocket of air or gas in the lung and includes blebs, bullae, pulmonary cysts, and lung cavities. Blebs and bullae can be classified by their wall thickness.

Airway basal cells are found deep in the respiratory epithelium, attached to, and lining the basement membrane.

Bronchoscopic lung volume reduction(BLVR) is a procedure to reduce the volume of air within the lungs. BLVR was initially developed in the early 2000s as a minimally invasive treatment for severe COPD that is primarily caused by emphysema. BLVR evolved from earlier surgical approaches first developed in the 1950s to reduce lung volume by removing damaged portions of the lungs via pneumonectomy or wedge resection. Procedures include the use of valves, coils, or thermal vapour ablation.

<span class="mw-page-title-main">Smoking-related interstitial fibrosis (SRIF)</span> Abnormal amount of collagen in the lung (fibrosis) caused by cigarette smoking

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