Dengue Fever

Introduction:

Dengue is a febrile illness caused by infection with one of four dengue viruses (DENV) transmitted by Aedes aegypti or Aedes albopictus mosquitoes during the taking of a blood meal. Infection may be asymptomatic or present with a broad range of clinical manifestations including a mild febrile illness to a life-threatening shock syndrome. Numerous viral, host, and vector factors are thought to impact risk of infection, disease, and disease severity.

There are four closely related but serologically distinct DENV types of the genus Flavivirus, called DENV-1, DENV-2, DENV-3, and DENV-4. There is transient cross-protection among the four DENVs, which weakens and disappears over the months following infection; therefore, individuals living in a dengue-endemic area with all types co-circulating are at risk for infection with any and all DENV types.

The Aedes mosquito:

Dengue viruses are transmitted by the bite of an infected female Aedes (subgenus Stegomyia) mosquito. Both males and females require nectar for energy. Females require a blood meal as a source of appropriate protein for egg development. Globally, Aedes aegypti is the predominant highly efficient mosquito vector for dengue infection, but the Asian tiger mosquito, Aedes albopictus, and other Aedes species can also transmit dengue with varying degrees of efficiency.

 Dengue fever :

DF (also known as "break-bone fever") is an acute febrile illness defined by the presence of fever and two or more of the following but not meeting the case definition of DHF. (see 'Dengue hemorrhagic fever' below):

●Headache

●Retro-orbital or ocular pain

●Myalgia and/or bone pain

●Arthralgia

●Rash

●Hemorrhagic manifestations (eg, positive tourniquet test, petechiae, purpura/ecchymosis, epistaxis, gum bleeding, blood in emesis, urine, or stool, or vaginal bleeding)

●Leukopenia   

Dengue hemorrhagic fever :

The cardinal feature of DHF is plasma leakage due to increased vascular permeability as evidenced by hemoconcentration (≥20 percent rise in hematocrit above baseline), pleural effusion, or ascites. DHF is also characterized by fever, thrombocytopenia, and hemorrhagic manifestations (all of which may also occur in the setting of DF). (See 'Dengue fever' above.)

In the setting of DHF, the presence of intense abdominal pain, persistent vomiting, and marked restlessness or lethargy, especially coinciding with defervescence, should alert the clinician to possible impending DSS. (See 'Dengue shock syndrome' below.)

The criteria for DHF comprise a narrow definition that does not encompass all patients with clinically severe or complicated DENV infections.

According to the guidelines, a DHF diagnosis requires all of the following be present:

●Fever or history of acute fever lasting 2 to 7 days, occasionally biphasic

●Hemorrhagic tendencies evidenced by at least one of the following:

•A positive tourniquet test – The tourniquet test is performed by inflating a blood pressure cuff on the upper arm to a point midway between the systolic and diastolic pressures for 5 minutes. A test is considered positive when 10 or more petechiae per 2.5 cm (1 inch) square are observed. The test may be negative or mildly positive during the phase of profound shock. It usually becomes positive, sometimes strongly positive, if the test is conducted after recovery from shock. It is estimated that the tourniquet test is positive in 80 percent of patients with dengue.

•Petechiae, ecchymoses, or purpura.

•Bleeding from the mucosa, gastrointestinal tract, injection sites, or other locations.

•Hematemesis or melena.

●Thrombocytopenia (100,000 cells per mm3 or less) – This number represents a direct count using a phase-contrast microscope (normal is 200,000 to 500,000 per mm3). In practice, for outpatients, an approximate count from a peripheral blood smear is acceptable. In healthy individuals, 4 to 10 platelets per oil-immersion field (100x; the average of the readings from 10 oil-immersion fields is recommended) indicates an adequate platelet count. An average of 3 platelets per oil-immersion field is considered low (ie, 100,000 per mm3).

●Evidence of plasma leakage due to increased vascular permeability manifested by at least one of the following:

•A rise in the hematocrit equal to or greater than 20 percent above average for age, sex, and population.

•A drop in the hematocrit following volume-replacement treatment equal to or greater than 20 percent of baseline.

•Signs of plasma leakage such as pleural effusion, ascites, and hypoproteinemia.

Dengue shock syndrome :

DSS is DHF with marked plasma leakage that leads to circulatory collapse (shock) as evidenced by narrowing pulse pressure or hypotension.

For a diagnosis of DSS, all of the above four criteria for DHF must be present plus evidence of circulatory failure manifested by:

●Rapid and weak pulse.

●Narrow pulse pressure (20 mmHg [2.7 kPa]) or manifested by:

•Hypotension for age – Hypotension is defined to be a systolic pressure 80 mmHg (10.7 kPa) for those less than 5 years of age or 90 mmHg (12.0 kPa) for those greater than or equal to 5 years of age. Note that narrow pulse pressure is observed early in the course of shock, whereas hypotension is observed later or in patients who experience severe bleeding.

•Cold, clammy skin and restlessness.

Dengue without warning signs:

A presumptive diagnosis of dengue infection may be made in the setting of residence in or travel to an endemic area plus fever and two of the following [9]:

●Nausea/vomiting

●Rash

●Headache, eye pain, muscle ache, or joint pain

●Leukopenia

●Positive tourniquet test

Dengue with warning signs :

Dengue with warning signs of severe infection includes dengue infection as defined above in addition to any of the following [9]:

●Abdominal pain or tenderness

●Persistent vomiting

●Clinical fluid accumulation (ascites, pleural effusion)

●Mucosal bleeding

●Lethargy or restlessness

●Hepatomegaly >2 cm

●Increase in hematocrit concurrent with rapid decrease in platelet count

Severe dengue :

Severe DENV infection includes infection with at least one of the following:

●Severe plasma leakage leading to:

•Shock

•Fluid accumulation with respiratory distress

●Severe bleeding (as evaluated by clinician)

●Severe organ involvement:

•Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥1000 units/L

•Impaired consciousness

•Organ failure

Signs and symptoms :

On average, dengue becomes symptomatic after a 4- to 10-day incubation period (range, 3-14 days). Dengue symptoms usually last 2-7 days.

Many individuals with dengue may be asymptomatic. Many patients with dengue experience a prodrome of chills; rash, including erythematous mottling of the skin; and facial flushing, which may last 2-3 days. Children younger than 15 years who have dengue usually have a nonspecific febrile syndrome, which may be accompanied by a maculopapular rash. Dengue should be suspected in individuals who present with high fever (104°F/40°C), retro-orbital headache, muscle and joint pain, nausea, lymphadenopathy, vomiting, and rash and who have traveled within 2 weeks of symptom onset to an area where appropriate vectors are present and dengue transmission may be occurring.

Accompanying symptoms in patients with dengue may include any of the following:

Fever

Headache

Retro-orbital pain

Severe myalgias: Especially of the lower back, arms, and legs

Arthralgias: Usually of the knees and shoulders

Nausea and vomiting (diarrhea is rare)

Rash: A maculopapular or macular confluent rash over the face, thorax, and flexor surfaces, with islands of skin sparing

Weakness, malaise, and lethargy

Altered taste sensation

Anorexia

Sore throat

Mild hemorrhagic manifestations (eg, petechiae, bleeding gums, epistaxis, menorrhagia, hematuria)

Lymphadenopathy

Diagnosis :

Demonstration of a fourfold or greater change in reciprocal immunoglobulin G (IgG) or IgM antibody titers to 1 or more dengue virus antigens in paired serum samples

Demonstration of dengue virus antigen in autopsy tissue via immunohistochemistry or immunofluorescence or in serum samples via enzyme immunoassay (MAC-ELISA, IgG ELISA, nonstructural protein 1 [NS1] ELISA, EIA)

Detection of viral genomic sequences in autopsy tissue, serum, or cerebral spinal fluid (CSF) samples via reverse-transcriptase polymerase chain reaction (RT-PCR) assay: RT-PCR provides earlier and more specific diagnosis.

Less frequently, isolation of the dengue virus from serum, plasma, leukocytes, or autopsy samples

PREVENTION :

Personal protection from infection

Mosquito repellants — Issues related to personal protection for prevention of mosquito bites are discussed separately. (See "Prevention of arthropod and insect bites: Repellents and other measures".)

Insecticide spraying — Distribution of insecticide-treated curtains was successful in reducing populations of A. aegypti mosquitoes for up to 18 months in several studies and was associated with reduced human and mosquito infections with DENV in one region, although use of the curtains declined with time. Insecticide spraying in response to dengue outbreaks is not highly effective, since A. aegypti mosquitoes frequently breed inside houses.

Vaccine development — Infection with one DENV type provides long-term protection against reinfection with that same type, supporting the feasibility of an effective dengue vaccine. 

Treatment :

No specific treatment for dengue fever exists.

While recovering from dengue fever, drink plenty of fluids. Call your doctor right away if you have any of the following signs and symptoms of dehydration:

Decreased urination

Few or no tears

Dry mouth or lips

Lethargy or confusion

Cold or clammy extremities

The over-the-counter (OTC) drug acetaminophen (Tylenol, others) can help reduce muscle pain and fever. But if you have dengue fever, you should avoid other OTC pain relievers, including aspirin, ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve). These pain relievers can increase the risk of dengue fever bleeding complications.

If you have severe dengue fever, you may need:

Supportive care in a hospital

Intravenous (IV) fluid and electrolyte replacement

Blood pressure monitoring

Transfusion to replace blood loss

Breast Cancer – Causes, Symptoms, Diagnosis & Treatment Options

 

Breast Cancer

Breast cancer is the common term for a set of breast tumor subtypes with distinct molecular and cellular origins and clinical behavior. Most of these are epithelial tumors of ductal or lobular origin (see the image below). Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the leading cause of cancer death among women.

 Risk Factors for Breast Cancer

Factors that may affect breast cancer risk include the following:

• Age: The strongest risk factor for breast cancer is age. Median age at diagnosis is about 60 years.

• Family history: Having a 1st-degree relative (mother, sister, daughter) with breast cancer doubles or triples risk of developing the cancer, but breast cancer in more distant relatives increases risk only slightly. When ≥ 2 1st-degree relatives have breast cancer, risk may be 5 to 6 times higher.

• Breast cancer gene mutation: About 5 to 10% of women with breast cancer carry a mutation in one of the two known breast cancer genes, BRCA1 or BRCA2. The risk of developing breast cancer by age 80 is about 72% with a BRCA1 mutation and about 69% with a BRCA2 mutation. Women with BRCA1 mutations also have an approximate 44% lifetime risk of developing ovarian cancer; risk among women with BRCA2 mutations is about 17% (3, 4). Women without a family history of breast cancer in at least two 1st-degree relatives are unlikely to carry this mutation and thus do not require screening for BRCA1 and BRCA2 mutations. Men who carry a BRCA mutation have a 1 to 2% lifetime risk of developing breast cancer. The mutations are more common among Ashkenazi Jews. Women with BRCA1 or BRCA2 mutations require closer surveillance or preventive measures, such as screening with both mammography and MRI, taking tamoxifen or raloxifene, or undergoing risk-reducing mastectomy.

• Personal history: Having had in situ or invasive breast cancer increases risk. Risk of developing cancer in the contralateral breast after mastectomy is about 0.5 to 1%/year of follow-up.

• Gynecologic history: Early menarche, late menopause, or late first pregnancy increases risk. Women who have a first pregnancy after age 30 are at higher risk than those who are nulliparous.

• Breast changes: History of a lesion that required a biopsy is associated with a slightly increased risk. Women with multiple breast masses but no histologic confirmation of a high-risk histology should not be considered at high risk. Benign lesions associated with a slightly increased risk of developing invasive breast cancer include complex fibroadenoma, moderate or florid hyperplasia (without atypia), sclerosing adenosis, and papilloma. Risk is about 4 or 5 times higher than average in patients with atypical ductal or lobular hyperplasia and about 10 times higher if they have a family history of invasive breast cancer in a 1st-degree relative. Increased breast density seen on screening mammography is associated with a 1.2- to 2.1-fold increased risk of breast cancer.

• Lobular carcinoma in situ (LCIS): Having LCIS increases the risk of developing invasive carcinoma in either breast by about 7 to 12 times ; invasive carcinoma develops in about 1 to 2% of patients with LCIS annually.

• Use of oral contraceptives: Study results vary regarding the use of oral contraceptives and risk of breast cancer. Some studies have found a small increased risk in current or recent users.

• Hormone therapy: Menopausal hormone (estrogen plus a progestin) therapy appears to increase risk modestly after only 3 years of use. After 5 years of use, the increased risk is about 7 or 8 more cases per 10,000 women for each year of use (about a 24% increase in relative risk). Use of estrogen alone does not appear to increase risk of breast cancer (as reported in the Women's Health Initiative). Selective estrogen-receptor modulators (eg, raloxifene) reduce the risk of developing breast cancer.

• Radiation therapy: Exposure to radiation therapy before age 30 increases risk. Mantle-field radiation therapy for Hodgkin lymphoma about quadruples risk of breast cancer over the next 20 to 30 years.

• Diet: Diet may contribute to development or growth of breast cancers, but conclusive evidence about the effect of a particular diet (eg, one high in fats) is lacking. Obese postmenopausal women are at increased risk, but there is no evidence that dietary modification reduces risk. For obese women who are menstruating later than normal, risk may be decreased.

• Lifestyle factors: Smoking and alcohol may contribute to a higher risk of breast cancer. Women are counseled to stop smoking and to reduce alcohol consumption. In epidemiologic studies, alcohol intake is associated with a higher risk of breast cancer; however, causality is difficult to establish. The American Cancer Society recommends no more than one alcoholic drink a day for women. 

• Pathology of Breast Cancer : 

• Most breast cancers are epithelial tumors that develop from cells lining ducts or lobules; less common are nonepithelial cancers of the supporting stroma (eg, angiosarcoma, primary stromal sarcomas, phyllodes tumor).
• Cancers are divided into carcinoma in situ and invasive cancer.

Carcinoma in situ is proliferation of cancer cells within ducts or lobules and without invasion of stromal tissue. There are 2 types:

Ductal carcinoma in situ (DCIS): About 85% of carcinoma in situ are this type. DCIS is usually detected only by mammography. It may involve a small or wide area of the breast; if a wide area is involved, microscopic invasive foci may develop over time.

Lobular carcinoma in situ (LCIS): LCIS is often multifocal and bilateral. There are 2 types: classic and pleomorphic. Classic LCIS is not malignant but increases risk of developing invasive carcinoma in either breast. This nonpalpable lesion is usually detected via biopsy; it is rarely visualized with mammography. Pleomorphic LCIS behaves more like DCIS; it should be excised to negative margins.

Invasive carcinoma is primarily adenocarcinoma. About 80% is the infiltrating ductal type; most of the remaining cases are infiltrating lobular.

Rare types include medullary, mucinous, metaplastic, and tubular carcinomas. Mucinous carcinoma tends to develop in older women and be slow growing. Women with most of these rare types of breast cancer have a much better prognosis than women with other types of invasive breast cancer. However, the prognosis for women with metaplastic breast cancer is significantly worse than other types of ductal breast cancer.

Inflammatory breast cancer is a fast-growing, particularly aggressive, and often fatal cancer. Cancer cells block the lymphatic vessels in breast skin; as a result, the breast appears inflamed, and the skin appears thickened, resembling orange peel (peau d’orange). Usually, inflammatory breast cancer spreads to the lymph nodes in the armpit. The lymph nodes feel like hard lumps. However, often no mass is felt in the breast itself because this cancer is dispersed throughout the breast.

Pathophysiology of Breast Cancer:

Breast cancer invades locally and spreads through the regional lymph nodes, bloodstream, or both. Metastatic breast cancer may affect almost any organ in the body—most commonly, lungs, liver, bone, brain, and skin. Most skin metastases occur near the site of breast surgery; scalp metastases are uncommon.

Hormone receptors:

Estrogen and progesterone receptors, present in some breast cancers, are nuclear hormone receptors that promote DNA replication and cell division when the appropriate hormones bind to them. Thus, drugs that block these receptors may be useful in treating tumors with the receptors. About two thirds of postmenopausal patients with cancer have an estrogen receptor–positive (ER+) tumor. Incidence of ER+ tumors is lower among premenopausal patients.

Another cellular receptor is human epidermal growth factor receptor 2 (HER2; also called HER2/neu or ErbB2); its presence correlates with a poorer prognosis at any given stage of cancer. In about 20% of patients with breast cancer, HER2 receptors are overexpressed. Drugs that block these receptors are part of standard treatment for these patients.

Breast cancer genes:

BRCA1 and BRCA2 gene mutations increase the risk of developing breast cancer to 70%. Prophylactic bilateral mastectomy reduces the risk of breast cancer by 90% and should be offered to women with a BRCA mutation. Other genetic mutations that increase the risk of developing breast cancer include mutations in CHEK2, PALB2, ATM, RAD51C, RAD51D, BARD1, and TP53, which are usually included in panel genetic testing.

Symptoms and Signs of Breast Cancer

Many breast cancers are discovered as a mass by the patient or during routine physical examination or mammography. Infrequently, the presenting symptom is breast enlargement or a nondescript thickening of the breast. Breast pain may be present but is almost never the sole presenting symptom of breast cancer.

Some types of breast cancer manifest with notable skin changes:

Paget disease of the nipple is associated with an underlying in situ or invasive carcinoma and manifests as skin changes, including erythema, crusting, scaling, and discharge; these changes usually appear so benign that the patient ignores them, delaying diagnosis for a year or more. About 50% of patients with Paget disease of the nipple have a palpable mass at presentation.

Inflammatory breast cancer manifests as erythema and enlargement of the breast, often without a mass, and skin may be discolored or appear thickened, resembling orange peel (peau d’orange). A nipple discharge is common.

A few patients with breast cancer present with signs of metastatic disease (eg, pathologic fracture, abdominal pain, jaundice, dyspnea).

A common finding during physical examination is asymmetry or a dominant mass—a mass distinctly different from the surrounding breast tissue. Diffuse fibrotic changes in a quadrant of the breast, usually the upper outer quadrant, are more characteristic of benign disorders; a slightly firmer thickening in one breast but not the other may be a sign of cancer.

More advanced breast cancers are characterized by one or more of the following:

Fixation of the mass to the chest wall or to overlying skin

Satellite nodules or ulcers in the skin

Matted or fixed axillary lymph nodes suggest tumor spread, as does supraclavicular or infraclavicular lymphadenopathy.

Change in breast size or shape

Skin dimpling or skin changes

Recent nipple inversion or skin change, or nipple abnormalities

Single-duct discharge, particularly if blood-stained

Axillary lump

    

 

Diagnosis of breast cancer

Breast cancer is often first detected as an abnormality on a mammogram before it is felt by the patient or health care provider.

1.Clinical examination

2.Imaging

3.Needle biopsy

4.Physical examination: The following physical findings should raise concern:

Lump or contour change

Skin tethering

Nipple inversion

Dilated veins

Ulceration

Paget disease

Edema or peau d’orange

Screening

Breast self-examination

Mammography

Ultrasonography

Magnetic resonance imaging

Treatment of Breast Cancer

Surgery

Usually radiation therapy

Systemic therapy: Endocrine therapy, chemotherapy, or both

 West Nile Infections Rising in the US

West Nile virus

West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family Flaviviridae, from the genus Flavivirus, which also contains the Zika virus, dengue virus, and yellow fever virus. The virus is primarily transmitted by mosquitoes, mostly species of Culex. The primary hosts of WNV are birds, so that the virus remains within a "bird–mosquito–bird" transmission cycle.The virus is genetically related to the Japanese encephalitis family of viruses.

Realm: Riboviria

Kingdom: Orthornavirae

Phylum: Kitrinoviricota

Class: Flasuviricetes

Order: Amarillovirales

Family: Flaviviridae

Genus: Flavivirus

Species: West Nile virus

Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States.

West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.

West Nile Virus is the leading cause of mosquito-borne disease in the continental US. And as of August 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention (CDC).

Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health, said, "Particularly here in California, it's peak risk right now."

She said scientists there are seeing higher mosquito and infected mosquito numbers.

"Peak Risk Right Now"

Dead birds are tested for the virus and by August 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by this time in 2022.

"Last year at this time, we had 60 positive dead birds out of 817 tested," Kramer said.

Severe flooding and high heat can contribute to the rise in mosquito populations and many parts of the country have seen plenty of both.

One of the ways scientists track infected mosquito patterns in California is by using flocks of strategically placed sentinel chickens.

"Chickens are a mosquito magnet," Kramer said.

Chickens don't get sick with the virus, but they do build antibodies to it. Surveillance teams check their blood every other week to track the virus.

Daniel Pastula, MD, MHS, chief of neuroinfectious diseases and global neurology at the University of Colorado School of Medicine and the Colorado School of Public Health, says the state is watching troubling signs as well.

"The concern this year," Pastula said, "particularly along the Front Range in Colorado, is we've found many more mosquitoes [that are] positive for West Nile earlier in the season compared with other years."

"We're bracing for higher-than-baseline human cases," he said.

Asked about this year's first human case reported in Toronto, Canada, a region with a long winter and low incidence of the virus, he said that provides a further example that people need to be prepared even in climates not known to be mosquito-dense.

He added, however, that climate is only one factor in the severity of the season. Others include birds' immunity and migratory patterns.

Pastula said that fluctuations in temperature and rainfall are rising with climate change and are disrupting normal baseline levels of West Nile.

"That shows we need to be prepared for West Nile virus and other mosquito-borne diseases in any place in North America or really the world. We recently saw malaria cases in the southern United States. It just shows you how dangerous mosquitoes can be."

Avoid Mosquito Bites

Pastula and Kramer list the precautions people can take to protect themselves from West Nile virus:

Limit outdoor exposure particularly at dusk and dawn

Wear protective clothing

Use EPA-approved insect repellent

Repair window screens so mosquitoes can't fly through

Dump and drain standing water on your property and maintain swimming pool

Pastula notes that summer is the time human cases start to mount — typically from July and August to the first hard freeze.

"We have been warning people here up and down the Front Range of Colorado to take prevention very seriously," Pastula said.

He pointed out that 80% who are infected with West Nile will have no symptoms.

About 20% will have flu-like illness — high fever, body and joint aches, rash, diarrhea, or headaches. Symptoms may last for weeks. About 1% of the time, he says, people can get neuroinvasive West Nile.

Pastula explains that the virus can infect the covering of the brain and spinal cord causing meningitis with very high fever, severe headaches, stiff neck, and sensitivity to light.

So far this year, there have been 89 neuroinvasive cases reported nationally, according to the CDC.

With West Nile encephalitis, the virus "can infect the brain itself causing altered mental status, movement disorders, or weakness," Pastula said.

Sometimes it can infect the gray matter of the spinal cord causing a West Nile virus poliomyelitis, which brings polio-like symptoms.

"The West Nile encephalitis and poliomyelitis can cause permanent deficits or even death," he said. "It's uncommon but it's not trivial."

Several vaccine candidates are in development, Pastula says, but none has reached clinical trials. Part of the reason for that, he says, is that scientists must be able to predict the timing of an outbreak.

"We're not really great at predicting outbreaks," he said.

Although the risk for neuroinvasive disease is small, it can be higher in certain groups, he says — those who are over age 60 years or are immunocompromised; those who have diabetes, cancer, or kidney disease; or those who have undergone organ transplants.

Those infected should see a healthcare professional and may be able to get relief with the usual medications for flu-like illness.

Some with severe infection may need to go to the hospital, Pastula said.

Asthma Pathophysiology, causes, symptoms & signs, prevention, diagnosis and treatment

 Airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

Pathophysiology:

1. Airway inflammation:

The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present. Some of the principal cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play an important role in the regulation of airway inflammation through the release of numerous cytokines. Other constituent airway cells, such as fibroblasts, endothelial cells, and epithelial cells, contribute to the chronicity of the disease. Other factors, such as adhesion molecules (eg, selectins, integrins), are critical in directing the inflammatory changes in the airway. Finally, cell-derived mediators influence smooth muscle tone and produce structural changes and remodeling of the airway.The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.Chronic inflammation of the airways is associated with increased bronchial hyperresponsiveness, which leads to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may be only partially reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and subepithelial fibrosis) that occurs with chronic untreated disease.Airway inflammation in asthma may represent a loss of normal balance between two "opposing" populations of Th lymphocytes. Two types of Th lymphocytes have been characterized: Th1 and Th2. Th1 cells produce interleukin (IL)-2 and IFN-α, which are critical in cellular defense mechanisms in response to infection. Th2, in contrast, generates a family of cytokines (IL-4, IL-5, IL-6, IL-9, and IL-13) that can mediate allergic inflammation. A study by Gauvreau et al found that IL-13 has a role in allergen-induced airway responses.

2. Intermittent airflow obstruction:

Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the consequence of immunoglobulin E-dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response. Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response. Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve. Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction. Airway obstruction causes increased resistance to airflow and decreased expiratory flow rates. These changes lead to a decreased ability to expel air and may result in hyperinflation. The resulting overdistention helps maintain airway patency, thereby improving expiratory flow; however, it also alters pulmonary mechanics and increases the work of breathing.

3. Bronchial hyperresponsiveness:

Hyperinflation compensates for the airflow obstruction, but this compensation is limited when the tidal volume approaches the volume of the pulmonary dead space; the result is alveolar hypoventilation. Uneven changes in airflow resistance, the resulting uneven distribution of air, and alterations in circulation from increased intra-alveolar pressure due to hyperinflation all lead to ventilation-perfusion mismatch. Vasoconstriction due to alveolar hypoxia also contributes to this mismatch. Vasoconstriction is also considered an adaptive response to ventilation/perfusion mismatch.In the early stages, when ventilation-perfusion mismatch results in hypoxia, hypercarbia is prevented by the ready diffusion of carbon dioxide across alveolar capillary membranes. Thus, patients with asthma who are in the early stages of an acute episode have hypoxemia in the absence of carbon dioxide retention. Hyperventilation triggered by the hypoxic drive also causes a decrease in PaCO2. An increase in alveolar ventilation in the early stages of an acute exacerbation prevents hypercarbia. With worsening obstruction and increasing ventilation-perfusion mismatch, carbon dioxide retention occurs. In the early stages of an acute episode, respiratory alkalosis results from hyperventilation. Later, the increased work of breathing, increased oxygen consumption, and increased cardiac output result in metabolic acidosis. Respiratory failure leads to respiratory acidosis due to retention of carbon dioxide as alveolar ventilation decreases.

Etiology:

Environmental allergens (eg, house dust mites; animal allergens, especially cat and dog; cockroach allergens; and fungi)

Viral respiratory tract infections

Exercise, hyperventilation

Gastroesophageal reflux disease

Chronic sinusitis or rhinitis

Aspirin or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity, sulfite sensitivity

Use of beta-adrenergic receptor blockers (including ophthalmic preparations)

Obesity

Environmental pollutants, tobacco smoke

Occupational exposure

Irritants (eg, household sprays, paint fumes)

Various high- and low-molecular-weight compounds (eg, insects, plants, latex, gums, diisocyanates, anhydrides, wood dust, and fluxes; associated with occupational asthma)

Emotional factors or stress

Perinatal factors (prematurity and increased maternal age; maternal smoking and prenatal exposure to tobacco smoke; breastfeeding has not been definitely shown to be protective)

Aspirin Induced Asthma:

The triad of asthma, aspirin sensitivity, and nasal polyps affects 5-10% of patients with asthma. Most patients experience symptoms during the third to fourth decade. A single dose can provoke an acute asthma exacerbation, accompanied by rhinorrhea, conjunctival irritation, and flushing of the head and neck. It can also occur with other nonsteroidal anti-inflammatory drugs and is caused by an increase in eosinophils and cysteinyl leukotrienes after exposure. Primary treatment is avoidance of these medications, but leukotriene antagonists have shown promise in treatment, allowing these patients to take daily aspirin for cardiac or rheumatic disease.  Aspirin desensitization has also been reported to decrease sinus symptoms, allowing daily dosing of aspirin.

Exercise Induced Asthma:

Exercise-induced asthma (EIA), or exercise-induced bronchoconstriction (EIB), is an asthma variant defined as a condition in which exercise or vigorous physical activity triggers acute bronchoconstriction in persons with heightened airway reactivity. It is observed primarily in persons who have asthma (exercise-induced bronchoconstriction in asthmatic persons) but can also be found in patients with normal resting spirometry findings with atopy, allergic rhinitis, or cystic fibrosis and even in healthy persons, many of whom are elite or cold weather athletes (exercise-induced bronchoconstriction in athletes). Exercise-induced bronchoconstriction is often a neglected diagnosis, and the underlying asthma may be silent in as many as 50% of patients, except during exercise.The pathogenesis of exercise-induced bronchoconstriction is controversial. The disease may be mediated by water loss from the airway, heat loss from the airway, or a combination of both. The upper airway is designed to keep inspired air at 100% humidity and body temperature at 37°C (98.6°F). The nose is unable to condition the increased amount of air required for exercise, particularly in athletes who breathe through their mouths. The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise. Results from bronchoalveolar lavage studies have not demonstrated an increase in inflammatory mediators. These patients generally develop a refractory period, during which a second exercise challenge does not cause a significant degree of bronchoconstriction.

Factors that contribute to exercise-induced bronchoconstriction symptoms (in both persons with asthma and athletes) include the following:

Exposure to cold or dry air

Environmental pollutants (eg, sulfur, ozone)

level of bronchial hyperreactivity

Chronicity of asthma and symptomatic control

Duration and intensity of exercise

Allergen exposure in atopic individuals

Coexisting respiratory infection

Clinical Presentation :

History:

Family history may be pertinent for asthma, allergy, sinusitis, rhinitis, eczema, and nasal polyps. The social history may include home characteristics, smoking, workplace or school characteristics, educational level, employment, social support, factors that may contribute to nonadherence of asthma medications, and illicit drug use.

Symptoms:

Wheezing, a musical, high-pitched, whistling sound produced by airflow turbulence, is one of the most common symptoms. In the mildest form, wheezing is only end expiratory. As severity increases, the wheeze lasts throughout expiration. In a more severe asthmatic episode, wheezing is also present during inspiration. During a most severe episode, wheezing may be absent because of the severe limitation of airflow associated with airway narrowing and respiratory muscle fatigue.

Asthma can occur without wheezing when obstruction involves predominantly the small airways. Thus, wheezing is not necessary for the diagnosis of asthma. Furthermore, wheezing can be associated with other causes of airway obstruction, such as cystic fibrosis and heart failure. Patients with vocal cord dysfunction, now referred to as inducible laryngeal obstruction (ILO), have a predominantly inspiratory monophonic wheeze (different from the polyphonic wheeze in asthma), which is heard best over the laryngeal area in the neck. Patients with excessive dynamic airway collapse (EDAC), bronchomalacia, or tracheomalacia also have an expiratory monophonic wheeze heard over the large airways. In exercise-induced bronchoconstriction, wheezing may be present after exercise, and in nocturnal asthma, wheezing is present during the night.

Cough may be the only symptom of asthma, especially in cases of exercise-induced or nocturnal asthma. Usually, the cough is nonproductive and nonparoxysmal. Children with nocturnal asthma tend to cough after midnight and during the early hours of morning. Chest tightness or a history of tightness or pain in the chest may be present with or without other symptoms of asthma, especially in exercise-induced or nocturnal asthma.

Other nonspecific symptoms in infants or young children may be a history of recurrent bronchitis, bronchiolitis, or pneumonia; a persistent cough with colds; and/or recurrent croup or chest rattling. Most children with chronic or recurrent bronchitis have asthma. Asthma is also the most common underlying diagnosis in children with recurrent pneumonia; older children may have a history of chest tightness and/or recurrent chest congestion.

Staging:

The severity of asthma is classified as the following:

Intermittent,

Mild persistent

Moderate persistent

Severe persistent

Patients with asthma of any level of severity may have mild, moderate, or severe exacerbations. Some patients with intermittent asthma have severe and life-threatening exacerbations separated by episodes with almost normal lung function and minimal symptoms; however, they are likely to have other evidence of increased bronchial hyperresponsiveness (BHR; exercise or challenge testing) due to ongoing inflammation.

Investigations:

1. Blood and sputum Eosinophils:

Blood eosinophilia greater than 4% or 300-400/μL supports the diagnosis of asthma, but an absence of this finding is not exclusionary. Eosinophil counts greater than 8% may be observed in patients with concomitant atopic dermatitis. This finding should prompt an evaluation for allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, or eosinophilic pneumonia.

2. Serum Immunoglobulin E:

Total serum immunoglobulin E levels greater than 100 IU are frequently observed in patients experiencing allergic reactions, but this finding is not specific for asthma and may be observed in patients with other conditions (eg, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome). A normal total serum immunoglobulin E level does not exclude the diagnosis of asthma. Elevated serum IgE levels are required for chronic asthma patients to be treated with omalizumab (Xolair).

3. Arterial Blood Gas:

Arterial blood gas (ABG) measurement provides important information in acute asthma. This test may reveal dangerous levels of hypoxemia or hypercarbia secondary to hypoventilation and, hence, respiratory acidosis. However, the typical finding in the early stages of an acute episode is respiratory alkalosis. Because of the accuracy and utility of pulse oximetry, only patients whose oxygenation is not restored to over 90% with oxygen therapy require an ABG. The clinical picture usually obviates ABGs for most ED patients with acute asthma.

Venous levels of PCO2 have been tested as a substitute for arterial measurements, and a venous PCO2 greater than 45 mm may serve as a screening test but cannot substitute for the ABG evaluation of respiratory function.

Hypercarbia is of concern in that it reflects inadequate ventilation and may indicate the need for mechanical ventilation if the PCO2 is elevated as a result of patient exhaustion; however, the decision to proceed with endotracheal intubation and mechanical ventilation is a clinical assessment.

4. Pulse oximeter:

Pulse oximetry measurement is desirable in all patients with acute asthma to exclude hypoxemia. The hypoxemia of uncomplicated acute asthma is readily reversible by oxygen administration. Oxygenation decreases 4-10 mm Hg with beta-agonist inhalant therapy due to increases in V/Q mismatch. Therefore, all patients with acute asthma should have oxygen saturation measured by pulse oximetry, or they simply should be placed on oxygen therapy.

5. Chest Radiography:

The chest radiograph remains the initial imaging evaluation in most individuals with symptoms of asthma. The value of chest radiography is in revealing complications or alternative causes of wheezing and the minor importance of wheezing in the diagnosis of asthma and its exacerbations. Chest radiography usually is more useful in the initial diagnosis of bronchial asthma than in the detection of exacerbations, although it is valuable in excluding complications such as pneumonia and asthma mimics, even during exacerbations.

In most patients with asthma, chest radiography findings are normal or may indicate hyperinflation. Findings may help rule out other pulmonary diseases such as allergic bronchopulmonary aspergillosis or sarcoidosis, which can manifest with symptoms of reactive airway disease. Chest radiography should be considered in all patients being evaluated for asthma to exclude other diagnoses.

Because pneumonia is one of the most common complications of asthma, chest radiography is indicated in patients with fever to rule out pneumonia. With new-onset asthma and eosinophilia, a radiograph may be useful in identifying prominent streaky infiltrates persisting less than 1 month, indicating Loeffler pneumonia. The infiltrates of Loeffler pneumonia are peripheral with central sparing of the lung fields. These findings have been described as the radiographic negative of pulmonary edema.

Patients with pleuritic chest pain or those with an acute asthmatic episode that responds poorly to therapy, require a chest film to exclude pneumothorax or pneumomediastinum, particularly if subcutaneous emphysema is present.

5. Chest CT Scanning:

HRCT findings in bronchial asthma include the following:

Bronchial wall thickening

Bronchial dilatation

Cylindrical and varicose bronchiectasis

Reduced airway luminal area

Mucoid impaction of the bronchi

Centrilobular opacities, or bronchiolar impaction

Linear opacities

Airtrapping, as demonstrated or exacerbated with expiration

Mosaic lung attenuation, or focal and regional areas of decreased perfusions

High-resolution CT scan of the thorax obtained during inspiration demonstrates airtrapping in a patient with asthma. Inspiratory findings are normal.

6. Skin Allergy Test:

Allergy skin testing is a useful adjunct in individuals with atopy. Results help guide indoor allergen mitigation or help diagnose allergic rhinitis symptoms. The allergens that most commonly cause asthma are aeroallergens such as house dust mites, animal danders, pollens, and mold spores. Two methods are available to test for allergic sensitivity to specific allergens in the environment: allergy skin tests and blood radioallergosorbent tests (RASTs). Allergy immunotherapy may be beneficial in controlling allergic rhinitis and asthma symptoms for some patients.

7. Pulmonary Function Test:

Spirometry assessments should be obtained as the primary test to establish the asthma diagnosis. Spirometry should be performed prior to initiating treatment in order to establish the presence and determine the severity of baseline airway obstruction.[62]Optimally, the initial spirometry should also include measurements before and after inhalation of a short-acting bronchodilator in all patients in whom the diagnosis of asthma is considered. Spirometry measures the forced vital capacity (FVC), the maximal amount of air expired from the point of maximal inhalation, and the forced expiratory volume in one second (FEV1). A reduced ratio of FEV1 to FVC, when compared with predicted values, demonstrates the presence of airway obstruction. Reversibility is demonstrated by an increase of 12% and 200 mL after the administration of a short-acting bronchodilator.

Differential Diagnosis:

Allergic and Environmental Asthma

Alpha1-Antitrypsin (AAT) Deficiency

Aspergillosis

Bronchiectasis

Bronchiolitis

Chronic Obstructive Pulmonary Disease (COPD)

Chronic Sinusitis

Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

Cystic Fibrosis

Exercise-Induced Anaphylaxis

Food-Dependent Exercise-Induced Anaphylaxis (FDEIA)

Foreign Body Aspiration

Gastroesophageal Reflux Disease

Heart Failure

Pediatric Airway Foreign Body

Pediatric Tracheomalacia

Pulmonary Embolism (PE)

Pulmonary Eosinophilia

Sarcoidosis

Upper Respiratory Tract Infection

Vocal Cord Dysfunction

Wheat-Dependent Exercise-Induced Anaphylaxis (WDEIA)

Treatment:

Step 1 for intermittent asthma is as follows:

Controller medication not indicated

Reliever medication is a short-acting beta-agonist (SABA) as needed for symptoms

Step 2 for mild persistent asthma is as follows:

Preferred controller medication is a low-dose inhaled corticosteroid

Alternatives include cromolyn, leukotriene receptor antagonist (LTRA),[110]or theophylline

Step 3 for moderate persistent asthma is as follows:

Preferred controller medication is either a low-dose inhaled corticosteroid (ICS) plus a long-acting beta-agonist (LABA) (combination medication is the preferred choice to improve compliance)or an inhaled medium-dose corticosteroid

Alternatives include a low-dose ICS plus either an LTRA or theophylline

Step 4 for moderate-to-severe persistent asthma is as follows:

Preferred controller medication is an inhaled medium-dose corticosteroid plus a LABA (combination therapy)

Alternatives include an inhaled medium-dose corticosteroid plus either an LTRA or theophylline

Step 5 for severe persistent asthma is as follows:

Preferred controller medication is an inhaled high-dose corticosteroid plus LABA

Step 6 for severe persistent asthma is as follows:

Preferred controller medication is an inhaled high-dose corticosteroid plus LABA plus oral corticosteroid.

Chronic Obstructive Pulmonary Disease (COPD)

 Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterised by persistent airflow limitation that is usually progressive, and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases.

COPD includes:

(1) Chronic Bronchitis (cough and sputum on most days for at least 3 months, in each of 2 consecutive years)

(2) Emphysema ( (abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis).

Risk Factors of COPD:

1. Environmenal:

• Tobacco smoke accounts for 95% of cases in UK

• Indoor air pollution; cooking with biomass fuels in confined

areas in developing countries

• Occupational exposures, such as coal dust, silica and

cadmium

• Low birth weight may reduce maximally attained lung

function in young adult life

• Lung growth: childhood infections or maternal smoking may

affect growth of lung during childhood, resulting in a lower

maximally attained lung function in adult life

• Infections: recurrent infection may accelerate decline in FEV1;

persistence of adenovirus in lung tissue may alter local

inflammatory response, predisposing to lung damage; HIV

infection is associated with emphysema

• Low socioeconomic status

• Cannabis smoking

2. Host 

• Genetic factors: α1-antiproteinase deficiency; other COPD

susceptibility genes are likely to be identified

• Airway hyper-reactivity

Clinical Presentation of COPD:

History:

Patients with chronic obstructive pulmonary disease (COPD) present with a combination of signs and symptoms of chronic bronchitis, emphysema, and asthma. Symptoms include worsening dyspnea, progressive exercise intolerance, and alteration in mental status. In addition, some important clinical and historical differences can exist between the types of COPD.

In the Chronic bronchitis group, classic symptoms include the following:

•Productive cough, with progression over time to intermittent dyspnea

•Frequent and recurrent pulmonary infections

•Progressive cardiac/respiratory failure over time, with edema and weight gain

In the Emphysema group, the history is somewhat different and may include the following set of classic symptoms:

•A long history of progressive dyspnea with late onset of nonproductive cough

•Occasional mucopurulent relapses

•Eventual cachexia and respiratory failure

Physical Examination of COPD:

Chronic bronchitis (blue bloaters) findings may be as follows:

•Patients may be obese.

•Frequent cough and expectoration are typical.

•Use of accessory muscles of respiration is common.

•Coarse rhonchi and wheezing may be heard on auscultation.

•Patients may have signs of right heart failure (ie, cor pulmonale), such as edema and cyanosis.

•Because they share many of the same physical signs, COPD may be difficult to distinguish from congestive heart failure (CHF). One crude bedside test for distinguishing COPD from CHF is peak expiratory flow. If patients blow 150-200 mL or less, they are probably having a COPD exacerbation; higher flows indicate a probable CHF exacerbation.

Emphysema (pink puffers) findings may be as follows:

•Patients may be very thin with a barrel chest.

•They typically have little or no cough or expectoration.

•Breathing may be assisted by pursed lips and use of accessory respiratory muscles; they may adopt the tripod sitting position. In this manner, the patient is trying to maintain a certain amount of positive end-expiratory pressure (PEEP) at the end of expiration, to help keep their lungs open, owing to the loss of lung structure from the disease.

•The chest may be hyperresonant, and wheezing may be heard; heart sounds are very distant.

•Overall appearance is more like classic COPD exacerbation.

Investigations for COPD:

1:Pulmonary Function Test (PFT):

Forced expiratory volume in 1 second (FEV1) is decreased, with concomitant reduction in FEV1/forced vital capacity (FVC) ratio. Patients have poor/absent reversibility with bronchodilators. FVC is normal or reduced. Total lung capacity (TLC) is normal or increased. Residual volume (RV) is increased. Diffusing capacity is normal or reduced.

2:Arterial Blood Gas (ABG's):

Arterial blood gas (ABG) analysis provides the best clues as to acuteness and severity. In general, renal compensation occurs even in chronic CO2 retainers (ie, bronchitics); thus, pH usually is near normal. Generally, consider any pH below 7.3 a sign of acute respiratory compromise.

3:CBC 

CBC may reveal polycythemia.

4:Chest Radiology

Chronic bronchitis is associated with increased bronchovascular markings and cardiomegaly.

Emphysema is associated with a small heart, hyperinflation, flat hemidiaphragms, and possible bullous changes. Typical findings are shown in the radiographs below.

Chronic obstructive pulmonary disease (COPD). A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on lateral chest radiograph.

Chronic obstructive pulmonary disease (COPD). A lung with emphysema shows increased anteroposterior (AP) diameter, increased retrosternal airspace, and flattened diaphragms on posteroanterior chest radiograph.

Spirometric classification of COPD severity based on post-bronchodilator FEV1

Stage                  Severity                 FEV1

I                         Mild*                    FEV1/FVC < 0.70

                                                        FEV1 ≥ 80% predicted

II                        Moderate              FEV1/FVC < 0.70

                                                        FEV1 50–79% predicted

III                      Severe                   FEV1/FVC < 0.70

                                                        FEV1 30–49% predicted

IV                     Very severe            FEV1/FVC < 0.70

                                                       FEV1 < 30% predicted or FEV1 < 50%

                                                       predicted if respiratory failure present

Management:

Prevention and maintenance therapy recommendations are as follows:

Smoking cessation is key. Pharmacotherapy and nicotine replacement increase long-term smoking abstinence rates, as do legislative bans on smoking. The effectiveness and safety of e-cigarettes as a smoking cessation aid is uncertain.

Pharmacologic therapy can reduce the symptoms of COPD, can reduce the severity and frequency of exacerbations, and can improve exercise tolerance and health status.

Pharmacologic treatment regimens should be individualized. They should be guided by symptom severity; exacerbation risk; adverse effects; comorbidities; drug availability and cost; and patient response, preference, and ability to utilize the various drug delivery devices.

Inhaler technique should be assessed regularly.

Pneumococcal and influenza vaccinations decrease the incidence of lower respiratory tract infections.

Pulmonary rehabilitation improves symptoms, physical and emotional participation in everyday activities, and quality of life.

Patients with severe resting chronic hypoxemia have improved survival with long-term oxygen therapy.

In patients with stable COPD and resting or exercise-induced moderate desaturation, routine long-term oxygen treatment is not recommended; however, consider individual patient factors regarding the need for supplemental oxygen.

With severe chronic hypercapnia and a history of hospitalization for acute respiratory failure, long-term noninvasive ventilation may prevent rehospitalization and decrease mortality.

Select patients with advanced emphysema refractory to optimized medical care may benefit from surgical or bronchoscopic interventional treatments.

In advanced COPD, palliative approaches are effective in controlling symptoms.

Exacerbation recommendations are as follows:

A COPD exacerbation is defined as acute respiratory symptom worsening with the need for additional therapy. Several factors can lead to an exacerbation, the most common being respiratory tract infections.

The recommended initial bronchodilators to treat an exacerbation are short-acting beta2-agonists, with or without short-acting anticholinergics.

As soon as possible before hospital discharge, initiate maintenance therapy with a long-acting bronchodilator.

Systemic corticosteroids can improve lung function and oxygenation. They also shorten recovery time and hospital duration. The duration of systemic corticosteroid therapy should not exceed 5-7 days.

If indicated, antibiotic therapy can shorten recovery time, reduce the risk of early relapse and treatment failure, and reduce hospitalization duration. The duration of antibiotic therapy should not exceed 5-7 days.

Owing to increased adverse effect profiles, methylxanthines are not recommended.

The first mode of ventilation used in COPD with acute respiratory failure and without contraindications is noninvasive mechanical ventilation. It improves gas exchange, reduces the work of breathing, decreases the need for intubation, decreases hospitalization duration, and improves survival.

GOLD patient grouping:

The GOLD patient group-based management recommendations include the following

Group A-D: Reduction of risk factors (influenza and pneumococcal vaccine); smoking cessation; physical activity; short-acting anticholinergic or short-acting beta-adrenergic agonists as needed

Group B: Long-acting anticholinergics or long-acting beta-adrenergic agonists; cardiopulmonary rehabilitation

Group C: Inhaled corticosteroid and long-acting beta-adrenergic agonists or long-acting anticholinergics; cardiopulmonary rehabilitation

Group D: Inhaled corticosteroid and long-acting beta-adrenergic agonists and/or long-acting anticholinergics; cardiopulmonary rehabilitation; long-term oxygen therapy (if criteria met); consider surgical options such as lung volume reduction surgery (LVRS)

Differential Diagnosis:

Acute Respiratory Distress Syndrome (ARDS)

Aspiration Pneumonitis and Pneumonia

Bacterial Pneumonia

Emergent Management of Pleural Effusion

Empyema and Abscess Pneumonia

Heart Failure

Mycoplasmal Pneumonia

Myocardial Infarction

Panic Disorder

Pneumonia in Immunocompromised Patients

Pneumothorax

Pulmonary Embolism (PE)

Viral Pneumoniae

Complications:

Incidence of pneumothorax due to bleb formation is relatively high; consider pneumothorax in all patients with COPD who have increased shortness of breath.

In patients who require long-term steroid use, the possibility of adrenal crisis is very real; at a minimum, patients with steroid-dependent COPD should receive stress dosing in the event of an exacerbation or any other stressor.

Infection (common)

Cor pulmonale

Secondary polycythemia

Bullous lung disease

Acute or chronic respiratory failure

Pulmonary hypertension

Malnutrition