Mesothelioma

Early mesothelioma symptoms like shortness of breath, pain in the chest, or fluid build-up around the lungs are easily confused with symptoms of other, less serious lung conditions.  Because of this, mesothelioma often goes undiagnosed and hence untreated until the late stages of the disease, when traditional therapies like radiation and chemotherapy are much less effective.  As with most cancers, the prognosis for patients with mesothelioma depends largely on how soon it is caught, and new tests are being developed to detect this life-threatening disease before it becomes untreatable.

Last September, researchers from a company called Somalogic Inc announced that they had found measurable changes in the blood of mesothelioma and pancreatic cancer patients.  Somalogic’s screening technology measured the presence of aptamers, a type of genetic material that adheres to proteins, in the blood of patients who had been diagnosed but not yet treated for these two types of cancer.  Unlike some other tests, these allowed doctors to distinguish between diseases with similar symptoms, such as pancreatic cancer versus pancreatitis and mesothelioma versus lung scarring.  The biological markers found in the blood were both specific and accurate.  More research is still needed to replicate these results and ensure their reliability, but this type of testing shows definite promise as an early screening method.

Another company, Rosetta Genomics, has been given approval in New York State to perform diagnostic tests of microRNA.  These biomarkers regulate protein creation and are highly tissue-specific, allowing doctors to use them to test for the primary tumor site for cancer that has metastasized, or spread throughout the body.  A test called “miRview meso” can help diagnose pleural mesothelioma, the most common type of the cancer, where the primary tumor is located in the lining of the chest cavity.  In addition to testing, there is some indication that microRNA can be manipulated to help slow the growth of tumors – a very important priority for cancers that develop as fast as mesothelioma does.

Since the cancer spreads so quickly, mesothelioma life expectancy is very low, with the five-year survival rate standing at around 10%.  However, new methods of testing for this disease are being developed all the time.  Though mesothelioma is nearly always caused by asbestos inhalation, a latency period of 20 to 50 years can elapse before symptoms begin to show.  It is therefore imperative that anyone whose job, such as factory work, ship building, or construction, brought them into contact with asbestos consult with a doctor about the possibility of asbestos-related disease.  Even if mesothelioma is not yet detectable, evidence of lung scarring can warn of potential future health complications.

Guest Article By – Eric Stevenson

His Chest X- ray shows diffuse ” Millet seed” lesions on Left side typical of Miliary Tuberculosis.

See the fullsize image –>> Photo focuses on “miliary TB’  seen in  left lung field . ( Right lung field excluded in the photo)

Miliary Tuberculosis of Lung : Typical "millet seed" lesions

Short Information about Miliary TB:

Blood-borne dissemination gives rise to miliary TB which may present acutely but more frequently is characterised by 2-3 weeks of

• fever,
• night sweats,
• anorexia,
• weightloss,
• dry cough,
• Hepatosplenomegaly may be present
• Headache may indicate co-existent TB-Meningitis.
• The classical X-ray appearance are those of 1-2 mm lesions (‘millet seed’) distributed through-out the lung fields, although occasionally the appearance are coarser.

Text Reference: Davidson’s Principal and Practice of Medicine.

Picture Credit : Sujit Shrestha

These are typical reference ranges, although various analysers and laboratories may employ different ranges.

Online Interpreter ABG : http://manuelsweb.com/abg.htm

Definition

COPD and Cigarette

Group of heterogeneous conditions embracing chronic bronchitis, chronic bronchiolitis (small airway disease) and emphysema characterized by air flow limitation that is not fully reversible.Emphysema is defined as enlargement of the distal airways with destruction of acinus , without associated fibrosis.Chronic bronchitis is defined clinically as cough, productive of at least 2 tablespoons of sputum on most days of 3 consecutive months in 2 consecutive years in the absence of other lung disease.Patients with a)emphysema on CT scan with normal spirometry or b) symptoms of chronic bronchitis and normal spirometry do not have COPD acc to current definition.

RISK FACTORS FOR DEVELOPMENT OF COPD

Exposures

Tobacco smoke-cigarette, pipe, cigar or Environmental Tobacco Smoke (ETS)

Biomass fuel fires (indoor air pollution)

Occupation-coal miners and those who work with cadmium

Outdoor and indoor air pollution

Low socioeconomic status

Low birth wt

Lung growth-insults including childhood infections or maternal smoking

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 associated with emphysema

Cannabis smoking (controversial)

Host factors

Genetic factors-a1-antiproteinase deficiency

Airway hyper-reactivity

PATHOPHYSIOLOGY

• Processes important in the pathogenesis of COPD include inflammation, imbalance of proteinases and antiproteinases in the lung, apoptosis and oxidative stress.
• Pathologic changes characteristic of COPD are found in the central airways, peripheral airways , lung parenchyma and pulmonary vasculature.
• Dilation and destruction of the terminal airways , structural changes in the airway wall due to inflammation, airway edema, and mucus hypersecretion contribute to the development of COPD.

Click to enlatge

Physiologic changes of the lungs characteristic of COPD include mucus hypersecretion , ciliary dysfunction, airflow limitation, pulmonary hyperinflation, alveolar gas exchange abnormalities and pulmonary vascular disease.

Clinical Presentation

a. Chronic cough

b. Chronic sputum production

c. Wheezing and chest discomfort.

d. Dyspnea-worse with exercise, Activities involving significant arm work,  particularly at or above shoulder level, are particularly difficult

e. persistent (+ everyday)

f. progressive increased effort to breath, air hunger, gasping, heaviness

g. Hx of exposure to risk factors-smoking

1-antitrypsin deficiency should be considered in patients with emphysema who had

a) A minimal smoking history

b) Early onset COPD

c) A family history of lung disease

d) A predominance of lower lobe emphysema

PHYSICAL EXAMINATION

In patients with more severe disease,prolonged exhalation , use of accessory muscle of respiration, chest hyperresonance to percussion, enlarged thoracic volume and decreased breath sounds.

Cyanosis

prolonged expiratory phase and expiratory wheezing. signs of hyperinflation include a barrel chest and enlarged lung volumes with poor diaphragmatic excursion as assessed by percussion. use of accessory muscles of respiration, sitting in the characteristic “tripod” position to facilitate the actions of the sternocleidomastoid, scalene, and intercostal muscles.

Marked tachypnea ,cyanosis and signs of increased work of breathing(paradoxical abdominal motion) may characterize a severe COPD exacerbation.

weight loss, bitemporal wasting, and diffuse loss of subcutaneous adipose tissue. poor prognostic factor in COPD.

paradoxical inward movement of the rib cage with inspiration (Hoover’s sign), the result of alteration of the vector of diaphragmatic contraction on the rib cage as a result of chronic hyperinflation.

LABORATORY STUDIES

1. A baseline ABG is often recommended for assessing patients.
2. ABGs detect acute and chronic hypercapnia and the development of acute respiratory acidosis may signal acute respiratory failure.
3. An elevated venous HCO3 may signify presence of a chronic respiratory acidosis.
4. An elevated haemoglobin may signify chronic hypoxemia.
5. Chest radiographs- thoracic hyperinflation, with flattening of diaphragm and increased retrosternal/retrocardiac air spaces, and hyperlucency with diminished vascular markings. bullae may be visible. to identify alternative diagnoses such as cardiac failure, other complications of smoking such as lung cancer

PHYSIOLOGIC TESTING

Spirometry: post-bronchodilator FEV1 less than 80% of the predicted value and accompanied by FEV1/FVC < 70%

Gold Criteria for COPD Severity

Stage I-mild-FEV₁/FVC <0.7 and FEV₁>80% predicted

Stage II-moderate-FEV₁/FVC <0.7 and 50% FEV₁ <80% predicted

Stage III-severe-FEV₁/FVC <0.7 and 30% FEV₁ <50% predicted

Stage IV-very severe-FEV₁/FVC <0.7 and FEV₁ <30% predicted

or

FEV₁ <50% predicted with respiratory failure or signs of right heart failure

When FEV1 falls to <1 L , the 5 year survival is approx 50%

Total lung capacity (TLC), functional residual capacity (FRC),and residual volume (RV) increase to supranormal values in patients with COPD indicating ling hyperinflation and air trapping.

Emphysema and many other diseases produce a reduction in the diffusing capacity of lung (DLCO)

TREATMENT

Long term management- smoking cessation and the correction of hypoxemia with supplemental oxygen produce the greatest survival benefit.

Medications

• Inhaled bronchodilators- beta -agonists and anticholinergics are the two main classes.
• Combination therapy (beta-agonists and anticholinergics) should be used in patients that did not achieve adequate relief with one class of drugs. Use of an MDI with a spacer or reservoir is as effective as delivery of the drug with nebulizer in most patients.
• Short acting inhaled beta2-agonists are used at two to four puffs bid-qid and PRN.
• Long acting-agonists salmeterol, formeterol or arformeterol are dosed twice daily.
• Short acting inhaled anticholinergics are used at two to four puffs bid-qid and PRN.
• Long acting anticholinergics tiotropium is dosed as one inhalation once daily.
• Methylxanthines:patient not responding to inhaled bronchodilator therapy may benefit from treatment with oral methylxanthine.sustained release theophylline is dosed once or twice daily . levels should be between 6 to 12 mg/L to avoid toxicity.
• Corticosteroids: Inhaled corticosteroids reduce the frequency and severity of exacerbations; they are currently recommended in patients with severe disease(FEV1<50%) who report two or more exacerbations requiring antibiotics or oral steroids per year. The combination of ICS with long acting ?-agonists produces further improvement in breathlessness and reduces the frequency and sverity of exacerbations.
• Systemic glucocorticoids are not recommended for long term management of COPD.

OXYGEN THERAPY

Long term domiciliary oxygen therapy(LTOT) used for 15hrs/day in patients with COPD and chronic severe hypoxemia improves survival, reduces secondary polycythaemia and prevents progression of primary pulmonary hypertension.

ADDITIONAL THERAPY

• Vaccinations: annual Influenza and Pneumococcal vaccinations reduce serious illness and mortality in patients with COPD.
• Intravenous -1 antitrypsin (A1AT) augmentation therapy may benefit select patients with A1AT deficiency and COPD.
• Mucolytics (e.g. acetylcysteine 200mg orally 8 hrly for 8 weeks in the first instance), antitussives, antioxidants ,antibiotics, vasodilators, respiratory stimulants have shown significant benefit.
• Chest physiotherapy
• Pulmonary rehabilitation
• Psychoactive drugs

SURGERY

• Surgical treatment options are
• Giant bullectomy
• Lung transplantation
• Lung volume reduction surgery

PROGNOSIS

A recent study has suggested that a composite score comprising the body mass index (B),the degree of airflow obstruction (O), a measurement of dyspnea (D) and exercise capacity (E) may assist in predicting death from respiratory and other causes.

ACUTE EXACERBATION OF COPD

Increased breathlessness, often accompanied by cough, sputum production, wheezing, chest tightness or other symptoms and signs of acutely worsened respiratory status define a COPD exacerbation.

Infection and air pollution are the most common causes.

D/D:

1. pneumothorax
2. Pneumonia
3. Aspiration
4. CHF
5. PE
6. Cardiac ischemia

Investigation: CXR ; ABG : Pao2<60mmhg, SpO2<90% when breathing room air- indicates respiratory failure

Moderate to severe acidosis pH<7.36 plus hypercapnia (PaCO2>50mmHg) In a pt with Respiratory failure is an indication for NIV/mechanical ventilation

Routine blood work , Oxyhemoglobin saturation

Indications for Hosp admission for AE

Marked increase in intensity of symptoms e.g. sudden development of resting dyspnea

Severe background copd

Onset of new physical signs eg cyanosis, peripheral edema

Failure of AE to respond to initial medical mgmt

Significant co morbidities

Freq AE

Newly occurring arrhythmias

Diagnostic uncertainty

Older age

Insufficient home support

Intensive Care Unit (ICU) admission

indications include severe dyspnea that does not adequately respond to therapy, mental status changes, and persistent or worsening hypoxemia, hypercapnia, or respiratory acidosis despite medical therapy.

MANAGEMENT:

Oxygen therapy -24-28% of oxygen at 2-4 l/min

Inhaled bronchodilators: short acting inhaled ?2 adrenergic agonists are the first line therapy for COPD exacerbations.

Short acting inhaled anticholinergic agents such as ipatropium bromide have similar efficacy .

Combined therapy is the most efficacious.

Antibiotics: indicated for patients with increased dyspnea, sputum volume and sputum purulence.

Haemophilus influenza, Streptococcus pneumonia and Moraxella catarrhalis are the most often causative agents.

Trimethoprim/sulfamethoxazole; amoxicillin ; azithromycin; co-amoxiclav; 2^nd or 3^rd generation cephalosporin are effective.

Corticosteroids:

Systemic corticosteroids Prednisone 30-40 mg PO daily

For patients with severe COPD exacerbation Prednisone 60 mg PO daily or IV methylprednisolone 60 mg IV q6h.

Mechanical ventilation:

Indications for invasive mechanical ventilation:-

Severe dyspnea with increased work of breathing, life threatening hypoxemia, respiratory acidosis, respiratory arrest, impaired mental status.

DISCHARGE CRITERIA

Use of inhaled bronchodilators less frequently than every 4 hrs ; clinical and ABG stability for at least 12-24hrs; acceptable ability to eat, sleep and ambulate ; adequate patient understanding of home therapy and adequate home arrangements.