Inflammatory Lung Diseases

Lung diseases are some of the most common medical conditions in the world.

Entities such as asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis are the result of ongoing inflammatory processes. Asthma is an ongoing disease of the bronchial tubes, where the airways overreact to external factors like smoke, air pollution, and allergens. The bronchial tubes become narrower due to the ensuing inflammation in the tissue lining the airways. This then produces the symptom of dyspnea, where the patient complains of trouble breathing and has difficulty moving air in and out of the lungs. Women are more likely than men to have asthma and are also more likely to die from it. COPD is another inflammatory disease where both the airways and lung tissue are affected. This can manifest as a combination of chronic obstructive bronchitis and emphysema, where the former is the result of chronic inflammation of the bronchial tubes and the latter is due to breakdown of the alveoli. COPD patients have difficulty moving air in and out of the lungs in addition to poor oxygen exchange. Pulmonary fibrosis is another chronic lung disease that is due to scarring or thickening of the lungs, which affects oxygen exchange. Often, the cause for pulmonary fibrosis is unknown.

Symptoms for lung disease can be subtle. An early sign of lung disease can be fatigue. Other signs are trouble breathing, shortness of breath, inability or decreased ability to exercise, coughing with or without blood or mucus, and pain when breathing in or out. For asthma, wheezing and chest tightness are common symptoms along with coughing and shortness of breath. COPD patients usually present with a chronic cough with large amounts of mucus production, as well as similar symptoms to that of asthma. Pulmonary fibrosis can produce a dry cough as well as fatigue, unexplained weight loss, and musculoskeletal pain.

The patient’s health history and physical exam is important to establish a basis for diagnosis. Patients are asked about any triggers such as allergens or pollutants and duration of exposure to external factors such as smoke or chemicals. To confirm diagnosis, imaging tests are the most helpful. Chest x-rays are the stalwart imaging test and can show scar tissue, lung hyperinflation, flattened hemidiaphragms, or bronchial wall thickening, depending on the disease entity. Computerized tomography scans, spirometry, arterial blood gas, and other tests may be appropriate depending on clinical presentation and history.

Causes of lung disease range from unknown to specific. COPD is most commonly caused by tobacco smoke, while asthma triggers can range from allergens, infections, cold air, or smoke. Lung disease entities like pulmonary fibrosis can pose a more difficult problem, as sometimes there may be a source but oftentimes the disease is idiopathic.

Therapies for lung disease can be effective in symptomatic treatment but not curative. Treatment initially consists of corticosteroids, beta agonists, leukotriene modifier or receptor antagonists, or methylxanthines like theophylline. In the early stages of lung disease, these medications can be given as monotherapy, but as the disease progresses, treatment is more likely to consist of multiple medications as well as supplemental oxygen and pulmonary rehabilitation. More than 35 million people in the United States live with some chronic lung disease and in 2014, it was estimated that the total cost of lung disease was around $154 billion annually. The costs could increase as COPD, currently the fourth leading cause of death worldwide, is projected to be the third leading cause of death by 2020. There is need for innovative and effective therapies that can slow the progress of lung disease.

Animal Models of Lung Disease

Pharma Models LLC offers a variety of different models of lung disease. A classic mouse model of lung disease comprises of using the chemotherapeutic glycopeptide bleomycin to induce interstitial pulmonary fibrosis like that in humans. This is the most commonly used experimental model for experimentally induce pulmonary fibrosis. For asthma, ovalbumin is a frequently used allergen for inducing allergic pulmonary inflammation like that found in asthma. To study acute lung exacerbation and injury that is common in chronic lung disease sufferers, bacterial lipopolysaccharide (LPS) is used to mimic such acute events.

Bleomycin model of Lung Disease

Bleomycin has commonly been used to induce pulmonary fibrosis in mice ever since it was seen to induce pulmonary fibrosis in humans. It can be used in a variety of experimental models, with mice being the most commonly used. It can be delivered by multiple methods, with intratracheal administration being the most frequently used route. Intraperitoneal, subcutaneous, intravenous, and inhalational can also be used. Regardless of how bleomycin is given, it directly injures lung cells via DNA strand breaks, free radicals and oxidative stress. Subsequent cell death occurs followed by inflammation and fibrosis. Bleomycin can induce fibrosis in as little as 2 to 4 weeks for an intratracheal model or 4 to 12 weeks in a systemic delivery model. C57BL/6 mice have proven to be more susceptible to the effects of bleomycin versus that of Balb/c mice.

Ovalbumin model of Lung Disease

Ovalbumin is frequently used to induce acute or chronic asthma in mice. The most commonly used mouse strain is the Balb/c mice, as they develop a Th2-based immunological response. C57BL/6 mice have also been used in successful allergen challenge studies. Acute sensitization protocols involve multiple systemic administrations along with an adjuvant, like aluminum hydroxide. Sensitization can take 14 to 21 days. Afterward, the mice are challenged with the allergen through the airway via inhalation as an aerosol or given intratracheally or intranasally.

For chronic asthma models, the mice are exposed to allergens such as ovalbumin for up to 12 weeks. These models are the model of choice for investigating the role of specific factors and cell types that are involved in the process of chronic inflammation. These also can be used to study structural changes in the airways due to chronic inflammation. They may also provide a system more conducive for the preclinical evaluation of novel therapeutic agents.

LPS model of Lung Disease

Bacterial lipopolysaccharide (LPS) is used because of its proinflammatory effects. When given chronically over several weeks, it can produce enlarged air spaces and other pathophysiological changes that resemble emphysema. Its most important use is to mimic acute exacerbations and injury that those with COPD are prone to develop. C57BL/6 mice receive intratracheal delivery of LPS installations.

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Inflammatory Diseases