Asthma is a common chronic inflammatory disease of the airways characterized by reversible airflow obstruction and bronchospasm.
Identify the triggers that cause asthma (reversible blockage of bronchi) attacks
- Symptoms of asthma include wheezing, coughing, chest tightness, and shortness of breath.
- Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic) and is thought to be caused by a combination of genetic and environmental factors.
- Treatment of acute symptoms is usually with an inhaled short-acting beta-2 agonist (such as salbutamol).
- asthma: A long-term respiratory condition, in which the airways may unexpectedly and suddenly narrow, often in response to an allergen, cold air, exercise, or emotional stress. Symptoms include wheezing, shortness of breath, chest tightness, and coughing.
- beta-2 agonist: β2-adrenergic agonists, also known as β2-adrenergic receptor agonists, are a class of drugs used to treat asthma and other pulmonary disease states.
- wheezing: A wheeze (formally called “sibilant rhonchi” in medical terminology) is a continuous, coarse, whistling sound produced in the respiratory airways during breathing. For wheezes to occur, some part of the respiratory tree must be narrowed or obstructed, or airflow velocity within the respiratory tree must be heightened.
Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath. The prevalence of asthma has been rising steadily since the early 1980s. Asthma is clinically classified according to the frequency of symptoms, forced expiratory volume over one second (FEV1), and peak expiratory flow rate. The latter can be measured with a peak flow meter. Asthma may also be classified as atopic (extrinsic) or non-atopic (intrinsic). It is thought to be caused by a combination of genetic and environmental factors. Treatment of acute symptoms is usually with an inhaled short-acting beta-2 agonist (such as salbutamol). Symptoms can be prevented by avoiding triggers such as allergens and irritants and by inhaling corticosteroids. Leukotriene antagonists are less effective than corticosteroids and thus less preferred. Its diagnosis is usually made based on the pattern of symptoms and/or response to therapy over time.
Although asthma is a chronic obstructive condition, it is not considered as a part of chronic obstructive pulmonary disease as this term refers specifically to irreversible combinations of disease such as bronchiectasis, chronic bronchitis, and emphysema. Unlike these diseases, the airway obstruction in asthma is usually reversible; however, if left untreated, the chronic inflammation from asthma can lead the lungs to become irreversibly obstructed due to airway remodeling. In contrast to emphysema, asthma affects the bronchi, not the alveoli.
An acute asthma exacerbation is commonly referred to as an asthma attack. The classic symptoms are shortness of breath, wheezing, and chest tightness. While these are the primary symptoms of asthma, in severe cases air motion may be significantly impaired such that no wheezing is heard. Signs that occur during an asthma attack include the use of accessory muscles of respiration (sternocleidomastoid and scalene muscles of the neck); there may be a paradoxical pulse (a pulse that is weaker during inhalation and stronger during exhalation) and over-inflation of the chest. A blue color of the skin and nails may occur from lack of oxygen.
Asthma is caused by environmental and genetic factors. These factors influence how severe asthma is and how well it responds to medication. For example, increased exposure to indoor allergens in infancy and early childhood has been analyzed as a primary cause of the rise in asthma. Primary prevention studies aimed at the aggressive reduction of airborne allergens in a home with infants have shown mixed findings. Strict reduction of dust mite allergens, for example, reduces the risk of allergic sensitization to dust mites, and modestly reduces the risk of developing asthma up until the age of 8 years old. However, studies also showed that the effects of exposure to cat and dog allergens worked in the converse fashion; exposure during the first year of life was found to reduce the risk of allergic sensitization and of developing asthma later in life. Similarly, many environmental risk factors have been associated with asthma development and morbidity in children. For example, recent studies show a direct relationship between increased exposure to air pollutants and incidence of childhood asthma. Lastly, viral respiratory infections (e.g., rhinovirus, Chlamydia pneumoniae) are both a leading trigger of asthma exacerbation and may increase the risk of developing asthma, especially in young children.
There is currently no precise physiologic, immunologic, or histologic test for diagnosing asthma. The diagnosis is usually made based on the pattern of symptoms (airways obstruction and hyperresponsiveness) and/or response to therapy (partial or complete reversibility) over time. The U.S. National Asthma Education and Prevention Program (NAEPP) uses a ‘symptom patterns’ approach. Their guidelines for the diagnosis and management of asthma state that a diagnosis of asthma begins by assessing for the presence of multiple key indicators such as wheezing, coughing, or viral infections which will increases the probability of a diagnosis of asthma. Spirometry is needed to establish a diagnosis of asthma.
Upon diagnosis, bronchodilators are recommended for short-term relief of symptoms. In those with occasional attacks, no other medication is needed. If mild persistent disease is present (more than two attacks a week), low-dose inhaled glucocorticoids or alternatively, an oral leukotriene antagonist or a mast cell stabilizer is recommended. For those who suffer daily attacks, a higher dose of inhaled glucocorticoid is used. In a severe asthma exacerbation, oral glucocorticoids are added to these treatments. Avoidance of triggers is a key component of improving control and preventing attacks. The most common triggers include allergens, smoke (tobacco and other), air pollution, non selective beta-blockers, and sulfite-containing foods. Cigarette smoking and second-hand smoke (passive smoke) may reduce the effectiveness of management medications such as steroid/corticosteroid therapies.
Respiratory Distress Syndrome
Acute respiratory distress syndrome (ARDS) is a serious reaction to various forms of injuries or acute infection to the lung.
Identify the factors involved in respiratory distress syndrome (RDS)
- ARDS is characterized by inflammation of the lung parenchyma leading to impaired gas exchange with concomitant systemic release of inflammatory mediators causing inflammation, hypoxemia, and frequently resulting in multiple organ failure.
- This condition is often fatal, usually requiring mechanical ventilation and admission to an intensive care unit.
- People with ARDS usually present with shortness of breath, tachypnea leading to hypoxia, and providing less oxygen to the brain occasionally causing confusion.
- acute respiratory distress syndrome: Acute respiratory distress syndrome (ARDS) is a serious reaction to various forms of injuries or acute infection to the lung. ARDS is a severe lung syndrome (not a disease) caused by a variety of direct and indirect issues.
Acute respiratory distress syndrome (ARDS), also known as respiratory distress syndrome (RDS) or adult respiratory distress syndrome, is a serious reaction to various forms of injuries or acute infection to the lung. ARDS is a severe lung syndrome (not a disease) caused by a variety of direct and indirect issues. It is characterized by inflammation of the lung parenchyma leading to impaired gas exchange with concomitant systemic release of inflammatory mediators causing inflammation, hypoxemia, and frequently resulting in multiple organ fail. This condition is often fatal, usually requiring mechanical ventilation and admission to an intensive care unit.
People with ARDS usually present with shortness of breath, tachypnea leading to hypoxia, and providing less oxygen to the brain occasionally causing confusion. ARDS can occur within 24 to 48 hours of an injury (trauma, burns, aspiration, massive blood transfusion, drug/alcohol abuse) or an acute illness (infectious pneumonia, sepsis, acute pancreatitis). It is characterized by bilateral infiltrates on chest radiograph sparing costophrenic angles and pulmonary artery wedge pressure < 18 mmHg (obtained by pulmonary artery catheterization).
Mechanical ventilation is an essential part of the treatment of ARDS to relieve respiratory muscles of their work, and to protect the usually obtunded patient’s airways. Ventilation is usually delivered through oro-tracheal intubation, or tracheostomy whenever prolonged ventilation (≥2 weeks) is deemed inevitable. However, mechanical ventilation may constitute a risk factor for the development, or the worsening, of ARDS.
Aside from the infectious complications arising from invasive ventilation with tracheal intubation, positive-pressure ventilation directly alters lung mechanics during ARDS. The result is higher mortality, i.e., through baro-trauma, when these techniques are used. If the underlying disease or injurious factor is not removed, the amount of inflammatory mediators released by the lungs in ARDS may result in a systemic inflammatory response syndrome (or sepsis if there is lung infection).
The evolution towards shock and/or multiple organ failure follows paths analogous to the pathophysiology of sepsis. This adds up to the impaired oxygenation which is the central problem of ARDS, as well as to respiratory acidosis, which is often caused by ventilation techniques such as permissive hypercapnia which attempt to limit ventilator-induced lung injury in ARDS. The result is a critical illness in which the “endothelial disease” of severe sepsis/SIRS is worsened by the pulmonary dysfunction, which further impairs oxygen delivery. Appropriate antibiotic therapy must be administered as soon as microbiological culture results are available. Empirical therapy may be appropriate if local microbiological surveillance is efficient.
Cystic fibrosis (CF) is an autosomal recessive disorder leading to respiratory congestion, multiple organ failure, and metabolic changes.
Evaluate the factors involved in cystic fibrosis (CF)
- Cystic fibrosis is characterized by abnormal transport of chloride and sodium across the epithelium, leading to thick, viscous secretions.
- CF is caused by a mutation in the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR), which is required to regulate the components of sweat, digestive juices, and mucus.
- The hallmark symptoms of cystic fibrosis are salty tasting skin, poor growth, poor weight gain despite a normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath.
- CFTR gene: The gene that encodes the CFTR protein is found on the human chromosome 7, on the long arm at position q31.2. from base pair 116,907,253 to base pair 117,095,955. CFTR orthologs have also been identified in all mammals for which complete genome data are available.
- cystic fibrosis: An inherited condition in which the exocrine glands produce abnormally viscous mucus, causing chronic respiratory and digestive problems.
- autosomal recessive: A mode of inheritance of genetic traits located on the allosomes (the sex determining chromosomes).
Cystic fibrosis (also known as CF or mucoviscidosis) is an autosomal recessive genetic disorder affecting most critically the lungs and also the pancreas, liver, and intestine. It is characterized by abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions. The name cystic fibrosis refers to the characteristic scarring (fibrosis) and cyst formation within the pancreas. Difficulty breathing is the most serious symptom and results from frequent lung infections that are treated with antibiotics and other medications. Other symptoms, including sinus infections, poor growth, and infertility affect other parts of the body. CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). The ΔF508 human genome mutation is characterized by the deletion of three base pairs in the CFTR nucleotide sequence, causing the loss of the amino acid phenylalanine located at position 508. This protein is required to regulate the components of sweat, digestive juices, and mucus. CFTR regulates the movement of chloride and sodium ions across epithelial membranes, such as the alveolar epithelia located in the lungs. Although most people without CF have two working copies of the CFTR gene, only one is needed to prevent cystic fibrosis due to the disorder’s recessive nature. CF develops when neither gene works normally (as a result of mutation) and therefore has autosomal recessive inheritance.
Diagnosis and Symptoms
CF is most common among caucasians and can be diagnosed before birth by genetic testing, or by a sweat test in early childhood. Ultimately, lung transplantation is often necessary as CF worsens. The hallmark symptoms of cystic fibrosis are salty tasting skin, poor growth, poor weight gain despite a normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Symptoms often appear in infancy and childhood, such as bowel obstruction due to meconium ileus in newborn babies.
Lung disease develops in CF as a result of clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. Inflammation and infection cause injury and structural changes to the lungs, leading to a variety of symptoms. In the early stages, incessant coughing, copious phlegm production, and decreased ability to exercise are common. Many of these symptoms occur when bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia. In later stages, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing.
Many CF patients are on one or more antibiotics at all times, even when healthy, to prophylactically suppress infection. Antibiotics are absolutely necessary whenever pneumonia is suspected or there has been a noticeable decline in lung function, and are usually chosen based on the results of a sputum analysis and the patient’s past response. Several mechanical techniques are used to dislodge sputum and encourage its expectoration. In the hospital setting, chest physiotherapy (CPT) is utilized. As lung disease worsens, mechanical breathing support may become necessary. Bi-lateral lung transplantation often becomes necessary for individuals with cystic fibrosis as lung function and exercise tolerance declines.
Gene therapy has been explored as a potential cure for cystic fibrosis. Ideally, gene therapy attempts to place a normal copy of the CFTR gene into affected cells. Transferring the normal CFTR gene into the affected epithelium cells would result in the production of functional CFTR in all target cells, without adverse reactions or an inflammation response. Studies have shown that to prevent the lung manifestations of cystic fibrosis, only 5–10% the normal amount of CFTR gene expression is needed.
Finally, a number of small molecules that aim at compensating various mutations of the CFTR gene are under development. About 10% of CF cases result from a premature stop codon in the DNA, leading to early termination of protein synthesis and truncated proteins. One approach to combating a faulty receptor is to develop drugs that get the ribosome to overcome this premature stop codon and synthesize a full-length CFTR protein.
Hypoxia, or hypoxiation, is inadequate oxygen supply to the body as a whole (generalized hypoxia) or a region of the body (tissue hypoxia).
Differentiate between hypoxia and hypoxemia
- A mismatch between oxygen supply and its demand at the cellular level may result in a hypoxic condition.
- Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia.
- Hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness leading to high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE).
- Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content.
- Hypoxia is a serious consequence of preterm birth in the neonate.
- In humans, hypoxia is detected by chemoreceptors in the carotid body, which override the signals from central chemoreceptors in the hypothalamus, increasing pO2 despite a falling pCO2.
- hyperventilation: The state of breathing faster or deeper than necessary.
- hypoxemia: An abnormal deficiency in the concentration of oxygen in the blood, be it the partial pressure of oxygen (mm Hg), the content of oxygen (ml oxygen per dl of blood) or the percent saturation of the blood’s hemoglobin, singly or in combination.
- anoxia: A condition in which tissues are severely or totally deprived of oxygen, severe hypoxia.
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole (generalized hypoxia) or a region of the body (tissue hypoxia) is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise. A mismatch between oxygen supply and its demand at the cellular level may result in a hypoxic condition. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia.
Hypoxia vs. Hypoxemia
Hypoxia differs from hypoxemia in that in the latter the oxygen concentration within the arterial blood is abnormally low. It is possible to experience hypoxia and have a low oxygen content (e.g., due to anemia) but maintain high oxygen partial pressure (pO2). Incorrect use of these terms can easily lead to confusion, especially as hypoxemia is among the causes of hypoxia (in hypoxemic hypoxia). Generalized hypoxia occurs in healthy people when they ascend to high altitude where it causes altitude sickness leading to potentially fatal complications: high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content, e.g., while diving underwater especially when using closed-circuit rebreather systems that control the amount of oxygen in the supplied air. A mild and non-damaging intermittent hypoxia is used intentionally during altitude trainings to develop an athletic performance adaptation at both the systemic and cellular level.
Hypoxia is also a serious consequence of preterm birth in the neonate. The main cause for this is that the lungs of the human fetus are among the last organs to develop during pregnancy. To assist the lungs to distribute oxygenated blood throughout the body, infants at risk of hypoxia are often placed inside an incubator capable of providing continuous positive airway pressure (also known as a humidicrib). In humans, hypoxia is detected by chemoreceptors in the carotid body. This response does not control ventilation rate at normal pO2, but below normal the activity of neurons innervating these receptors increases dramatically, so much so to override the signals from central chemoreceptors in the hypothalamus, increasing pO2 despite a falling pCO2.
Hypoxemic hypoxia is a generalized hypoxia, with an inadequate supply of oxygen to the body as a whole. The term “hypoxemic hypoxia” specifies hypoxia caused by low partial pressure of oxygen in arterial blood. In the other causes of hypoxia that follow, the partial pressure of oxygen in arterial blood is normal. Hypoxemic hypoxia may be due to hypoventilation or inadequate pulmonary minute ventilation (e.g., respiratory arrest or by drugs such as opiates).
Symptoms of Hypoxia
The symptoms of generalized hypoxia depend on its severity and acceleration of onset. In the case of altitude sickness, where hypoxia develops gradually, the symptoms include headaches, fatigue, shortness of breath, a feeling of euphoria, and nausea. In severe hypoxia, or hypoxia of very rapid onset, changes in levels of consciousness, seizures, coma, priapism, and death occur. Severe hypoxia induces a blue discoloration of the skin, called cyanosis. Because hemoglobin is a darker red when it is not bound to oxygen (deoxyhemoglobin), as opposed to the rich red color that it has when bound to oxygen (oxyhemoglobin), when seen through the skin it has an increased tendency to reflect blue light back to the eye. In cases where the oxygen is displaced by another molecule, such as carbon monoxide, the skin may appear “cherry red” instead of cyanotic.
Body’s Response to Hypoxia
In most tissues of the body, the response to hypoxia is vasodilation. By widening the blood vessels, the tissue allows greater perfusion. By contrast, in the lungs, the response to hypoxia is vasoconstriction. This is known as “Hypoxic pulmonary vasoconstriction” or “HPV.” To counter the effects of high-altitude diseases, the body must return arterial pO2 toward normal. Acclimatization, the means by which the body adapts to higher altitudes, only partially restores pO2 to standard levels. Hyperventilation, the body’s most common response to high-altitude conditions, increases alveolar pO2 by raising the depth and rate of breathing.
However, while pO2 does improve with hyperventilation, it does not return to normal. Studies of miners and astronomers working at 3,000 meters and above show improved alveolar pO2 with full acclimatization, yet the pO2 level remains equal to or even below the threshold for continuous oxygen therapy for patients with chronic obstructive pulmonary disease (COPD). In addition, there are complications involved with acclimatization. Polycythemia, in which the body increases the number of red blood cells in circulation, thickens the blood, raising the danger that the heart can’t pump it.