Emphysema and chronic bronchitis are airflow-limited states contained within the disease state known as chronic obstructive pulmonary disease (COPD). Just as asthma is no longer grouped with COPD, the current definition of COPD put forth by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) also no longer distinguishes between emphysema and chronic bronchitis. 
Emphysema is pathologically defined as an abnormal permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by the destruction of alveolar walls and without obvious fibrosis. Clinically, the term emphysema is used interchangeably with chronic obstructive pulmonary disease, or COPD.
The theory surrounding this definition has been around since the 1950s, with a key concept of irreversibility and/or permanent acinar damage. However, new data posit that increased collagen deposition leads to active fibrosis, which inevitably is associated with breakdown of the lung’s elastic framework. An entity known as combined pulmonary fibrosis and emphysema (CPFE) has been shown to exist in a subset of emphysematous patients.  This implies an association between fibrosis and the permanence of alveolar damage. The complex mechanism thought to be responsible is the interplay between Notch and Wnt, two signaling pathways playing critical roles in epithelial and mesenchymal precursor cell maintenance and differentiation. 
Discussions on how obstructive diseases share similar phenotypes have been emerging and evolving within the literature. Asthma and chronic obstructive pulmonary disease overlap syndrome (ACOS) is a term that is finding its way into journals and literature reviews. This entity seeks to describe patients who have severe COPD and/or severe asthma who find themselves with frequent exacerbations/hospitalizations and difficult-to-control or refractory symptoms. Although not clearly defined as of yet, ACOS encompasses a challenge to answer, specifically because of the lack of evidence-based guidelines to support its naming, recognition, and management. 
The risk factors thought to be responsible for the development of COPD are all associated with an accelerated decline in FEV1 over time. Leading this list is cigarette smoking: 15-20% of 1 pack-per-day smokers and 25% of 2 pack-per-day smokers develop COPD. Next are cigars and pipe smoke, followed by secondhand and thirdhand smoke. Occupational, inhalational, and environmental exposures, including biomass fuel cooking, also are included on the list. 
Women in developing countries who are exposed to biomass cooking of liquids and fuels, including wood, crops, animal dung, and coal, are at increased risk of developing COPD. Add to that poor ventilation of the home and dependent family members’ (children and elderly persons) risk also increases. Throughout the world, COPD is a disease of occupation and environmental pollutants too, including but not limited to organic and inorganic dusts, isocyanates, and phosgenes. 
The latest systematic review looked at the impact of air pollution on COPD sufferers (inclusive of articles prior to 1990); the investigators concluded that the need to continue to improve air quality guidelines is more important than ever as biomass cooking in low-income nations was clearly associated with COPD mortality in adult female nonsmokers  .
However, the evolution of disease based on smoke exposure differs widely among people, suggesting genetic factors to be involved. It is not truly known why certain people with a positive smoke exposure develop injury patterns, symptoms, and disease. For instance, the Lung Health Study from 2002 showed that a third of smokers never developed impaired lung function after 11 years despite a baseline study of airway obstruction. 
Genetic risk factors for the development of COPD are also thought to exist. The most well-studied is alpha-1-antitrypsin (AAT) deficiency (also known as alpha-1 antiprotease deficiency).
AAT is a glycoprotein member of the serine protease inhibitor family that is synthesized in the liver and is secreted into the blood stream. The main purpose of this 394–amino acid, single-chain protein is to neutralize neutrophil elastase in the lung interstitium and to protect the lung parenchyma from elastolytic breakdown. If not inactivated by AAT, neutrophil elastase destroys lung connective tissue leading to emphysema. Therefore, severe AAT deficiency predisposes to unopposed elastolysis with the clinical sequela of an early onset of panacinar emphysema.
Deficiency of AAT is inherited as an autosomal codominant condition. The gene, located on the long arm of chromosome 14, expresses different phenotypes (serum protease inhibitor phenotype notated Pi type). The most common type of severe AAT phenotype (more than 90%) occurs in individuals who are homozygous for the Z allele. Homozygous individuals (Pi ZZ), usually of northern European descent, have serum levels well below the reference range levels at about 20% of the normal level (2.5 to 7 mmol/L). The normal M allele phenotype is Pi MM, with levels of 20-48 mmol/L. 
Lifetime nonsmokers who are homozygous for the Z allele rarely develop emphysema. Hence, cigarette smoking is the most important risk factor for emphysema development. The American Thoracic Society/European Respiratory Society (ATS/ERS) Guidelines  recommend screening for AAT deficiency if emphysema is suspected in any patient younger than 45 years and with any of the following:
Absence of recognized emphysema risk factors such as smoking or occupational inhalational exposure
Unexplained liver disease
Family history of AAT deficiency, COPD, bronchiectasis, or panniculitis
Positive c-ANCA (anti-neutrophilic cytoplasmic antibody) vasculitis
Asthma with persistent, fixed-airways obstruction despite therapy
Once innate respiratory defenses of the lung’s epithelial cell barrier and mucociliary transport system are infiltrated by foreign/invading antigens (noxious cigarette ingredients, for instance), the responding inflammatory immune cells (including polymorphonuclear cells, eosinophils, macrophages, CD4 positive and CD8 positive lymphocytes) transport the antigens to the bronchial associated lymphatic tissue layer (BALT). It is here where the majority of the release of neutrophilic chemotactic factors is thought to occur. Proteolytic enzymes like matrix-metalloproteinases (MMPs) are mainly released by macrophages, which lead to destruction of the lung’s epithelial barrier.
Macrophages are found to be 5- to 10-fold higher in the bronchoalveolar lavage fluid of emphysematous pateints.  Also, along with macrophages, the release of proteases and free radical hydrogen peroxide from neutrophils adds to the epithelial ruination, specifically with emphasis on the basement membrane. This is why neutrophils are thought to be highly important in the pathogenesis of emphysema at the tissue level, a differentiator to the mainly eosinophilic inflammatory response in airways affected by asthma.
After all, the T lymphocytes in the sputum of emphysematous smokers are mainly CD8 positive cells.  These cells release chemotactic factors to recruit more cells (pro-inflammatory cytokines that amplify the inflammation) and growth factors that promote structural change. The inflammation is further amplified by oxidative stress and protease production. Oxidants are produced from cigarette smoke and released from inflammatory cells. Proteases are produced by inflammatory, macrophage, and epithelial cells, which fuel bronchiolar edema from an elastin-destroying protease-antiprotease imbalance. This protease-menace is elastase, released by macrophages, and responsible for breakdown of the lung’s fragile elastic lamina (of which elastin is a structural protein component).  This is believed to be central in the development of emphysema. Peptides from elastin can be detected in increased quantities in patients with emphysema and AAT. 
The repair process of airway remodeling further exacerbates emphysema’s anatomical derangements with key characters such as vascular endothelial growth factor (VEGF), which is expressed in airway smooth muscle cells and is responsible for neovascularization and expression of increased and possibly abnormal patterns of fibroblastic development. It is these structural changes of mucus hyperplasia, bronchiolar edema, and smooth muscle hypertrophy and fibrosis in smokers’ airways that result in the small airways narrowing of less than two millimeters.
Pathologically defined as permanent enlargement of airspaces distal to the terminal bronchioles, emphysema creates an environment leading to a dramatic decline in the alveolar surface area available for gas exchange. Loss of individual alveoli with septal wall destruction leads to airflow limitation via two mechanisms. First, loss of alveolar wall results in a decrease in elastic recoil, which subsequently limits airflow. Second, loss of alveolar supporting structures is indirectly responsible for airway narrowing, again limiting airflow. 
Though the paradigm for classification continues to evolve, the described morphological pathology of region-specific emphysema remains in three types: 
Centriacinar emphysema is the most common type of pulmonary emphysema mainly localized to the proximal respiratory bronchioles with focal destruction and predominantly found in the upper lung zones. The surrounding lung parenchyma is usually normal with untouched distal alveolar ducts and sacs. Also known as centrilobular emphysema, this entity is associated with and closely-related to long-standing cigarette smoking and dust inhalation. [15, 16]
Panacinar emphysema destroys the entire alveolus uniformly and is predominant in the lower half of the lungs. Panacinar emphysema generally is observed in patients with homozygous (Pi ZZ) alpha1-antitrypsin (AAT) deficiency. In people who smoke, focal panacinar emphysema at the lung bases may accompany centriacinar emphysema. [15, 16]
Paraseptal emphysema, also known as distal acinar emphysema, preferentially involves the distal airway structures, alveolar ducts, and alveolar sacs. The process is localized around the septae of the lungs or pleura. Although airflow is frequently preserved, the apical bullae may lead to spontaneous pneumothorax. Giant bullae occasionally cause severe compression of adjacent lung tissue. [15, 16]
The National Health Interview Survey reports the prevalence of emphysema at 18 cases per 1000 persons and chronic bronchitis at 34 cases per 1000 persons.  While the rate of emphysema has stayed largely unchanged since 2000, the rate of chronic bronchitis has decreased. This prevalence is based on the number of adults who have ever been told by any health care provider that they have emphysema or chronic bronchitis. This is felt to be an underestimation because most patients do not present for medical care until the disease is in its later stages.
The Burden of Obstructive Lung Disease (BOLD) study showed that the worldwide prevalence of COPD (stage II or higher) was 10.1%.  This figure varied by geographic location and by sex with a pooled prevalence among men of 11.8% (8.6-22.2%) and among women of 8.5% (5.1-16.7%). The differences can, in part, be explained by site and sex differences in the prevalence of smoking. These rates are similar to rates observed in the Proyecto Latino Americano de Investigacion en Obstruccion Pulmonar (PLATINO study), which studied 5 countries in Latin America. 
In the past, COPD was more prevalent among men; however, this was attributed to the difference in smoking rates of men versus women. With the increase in smoking among women over the past 30 years, the sex difference has declined. Some studies have suggested women may be even more susceptible to the development of emphysema. [20, 21]
Various measures have been shown to correlate with prognosis in COPD, including forced expiratory volume in 1 second (FEV1), diffusion capacity for carbon monoxide (DLCO), blood gas measurements, body mass index (BMI), exercise capacity, and clinical status. A correlation has also been established between radiographic severity of emphysema and mortality. 
A widely used simple prognostication tool is the BODE index, which is based on the BMI, obstruction (FEV1), dyspnea (using Medical Research Council Dyspnea Scale), and exercise capacity (ie, 6-minute walk distance).
Body mass index is scored as follows:
Greater than 21 = 0 points
Less than 21 = 1 point
FEV1 (postbronchodilator percent predicted) is scored as follows:
Greater than 65% = 0 points
50-64% = 1 point
36-49% = 2 points
Less than 35% = 3 points
Modified Medical Research Council (MMRC) dyspnea scale is scored as follows:
MMRC 0 = Dyspneic on strenuous exercise (0 points)
MMRC 1 = Dyspneic on walking a slight hill (0 points)
MMRC 2 = Dyspneic on walking level ground; must stop occasionally due to breathlessness (1 point)
MMRC 3 = Dyspneic after walking 100 yards or a few minutes (2 points)
MMRC 4 = Cannot leave house; dyspneic doing activities of daily living (3 points)
Six-minute walking distance is scored as follows:
Greater than 350 meters = 0 points
250-349 meters = 1 point
150-249 meters = 2 points
Less than 149 meters = 3 points
BODE's approximate 4-year survival is as follows:
0-2 points = 80%
3-4 points = 67%
5-6 points = 57%
7-10 points = 18%
A US Centers for Disease Control and Prevention (CDC) Morbidity Mortality Weekly Report study of the National Vital Statistics System reported an age-standardized death rate from COPD in the United States for adults older than 25 years of 64.3 deaths per 100,000 population.  This rate varied by location, with the lowest rate in Hawaii (27.1 deaths per 100,000 population) and the highest rate in Oklahoma (93.6 deaths per 100,000 population).
Many commercial airplanes fly at altitudes of 30,000-40,000 feet, but passenger cabins are pressurized to an altitude of 5,000-8,000 feet. At these altitudes, atmospheric partial pressure of oxygen (PO2) is 132-109 mm Hg, compared with 159 mm Hg at sea level. Acute reduction in PO2 stimulates peripheral chemoreceptors, which results in hyperventilation. Usually, this increase in tidal volume (caused by increase in minute ventilation) is subtle and not recognized by the healthy population. In patients with COPD and emphysema, it may be noticeable. The following is a prediction equation used to estimate PaO2 at 8000 feet (2440 m):
PaO2 = 22.8 - 2.74x + 0.68y
x = Altitude
y = Arterial PO2 at sea level
A predicted PaO2 of 50 mm Hg or less at an altitude of 8,000 feet is an indication for supplemental oxygen. This can be arranged prior to the flight through the airline directly or through the airline agent but requires extra expense. 
Sleep and COPD
Patients with COPD may develop substantial decreases in nocturnal PaO2 during all phases of sleep but particularly during rapid eye movement sleep. These episodes are associated with rises in pulmonary arterial pressures and disturbance in sleep architecture initially, but patients may develop pulmonary arterial hypertension and cor pulmonale if the hypoxemia remains untreated. Therefore, patients who have a daytime PaO2 greater than 60 mm Hg but demonstrate substantial nocturnal hypoxemia should be prescribed oxygen supplementation for use during sleep.
What would you like to print?