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4/27/2015
Pulmonary Medicine
ETSU Internal Medicine Board Review
Thomas Roy, MD
PFTs ‐ The Essentials
PFTs ‐ The Essentials
• Spirometry determines patency of the tubes) : • Diagnoses Obstructive diseases
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–
–
–
Expiratory Flows
Flow‐Volume Loops
Response to Bronchodilators
Response to Bronchoprovocation
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Expiratory Flows
• FEV1/FVC < 70% defines Obstruction – FVC – the maximal amount of air that can be forcibly exhaled
– FEV1 – the volume exhaled during the first second of a forced vital capacity ( FVC)
Expiratory Flows
• The degree of obstruction is determined by comparing the measured FEV1 to the FEV1 predicted
• Predicted values determined by age, height, gender, ethnicity
• Normal: > 0.8
• “Mild” “Moderate” “Severe” (ATS, EU, BTS) • GOLD criteria for exam
PFTs ‐ The Essentials
• Lung Volumes determine the elasticity of parenchyma • Diagnoses Restrictive diseases
• Diseases that affect the prenchyma or chest wall
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Restrictive Lung Disease
• Small lungs with increased stiffness from parenchymal disease or scarring
• FEV1 and FVC are each decreased
• However, decreased proportionately so FEV1/FVC ratio is preserved
Dynamic Lung Volumes
Obstructive
Restrictive
FVC
FEV1
FEV1/FVC
< 70%
> 70%
FVC = Force Vital Capacity
FEV1 = Forced Expiratory Volume in 1 second
Response to Bronchodilators
• Use inhaled B2‐agonist in obstruction to check for response
• Significant response = Bronchial hyper‐
reactivity (BHR)
• Improvement in FEV1 or FVC from baseline by 12% and 200 cc
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Pulmonary Function Test:
Spirometry
Flow (L/s)
Inspiratory Expiratory
Volume Vs Time
FEV1
PEFR
FEF 25%
FEF 50%
FEF 75%
0 0
IRV Vt ERV RV
FVC
FRC
TLC
Lung Volumes and Capacities
PFTs ‐ The Essentials
Pulmonary Function Test:
Intrathoracic / Extrathoracic Obstruction
Flow (L/s)
Inspiratory Expiratory
FEF50
FIF50
FEF50 / FIF50
<1 >1 1
Intrathoracic Extrathoracic Fixed
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Flow‐Volume in UAO • Dynamic Extrathoracic: obstruction on inspiration:
– tracheomalacia
– vocal cord problem
Fixed Upper Airway Obstruction
• Both inspiratory and expiratory loops are flattened – compressive tumors – tracheal stenosis –
“prolonged intubation”
DLCO
• Pt exposed to a known concentration of CO for a known time
• New concentration of CO allows calculation of transfer speed
• CO to Hgb
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Diagnose pulmonary disease Chronic
Bronchitis
Emphysema
Pulmonary
Fibrosis
Pulmonary
FEV1/FVC
↓
↓
↑
nl
TLC
nl
↑
↓
nl
DLCO
nl
↓
↓
↓
hypertension
Asthma
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Asthma
• Asthma afflicts 6% to 8% of the United States population, making it one of the most common chronic diseases in the country • And so, the ABIM will ask you a lot of questions about asthma
Asthma ‐ essentials
The disease is characterized by: • Episodic airflow obstruction that is reversible
• Bronchial hyperresponsiveness (BHR) to a variety of stimuli
• Persistent lung inflammation, particularly in the airways
• A multifactorial etiology
• A genetic predisposition
PFT Patterns
• Reduced expiratory flow (FEV1/FVC <70%)
• Significant FEV1 response to bronchodilator
(12% from baseline or 200cc increase)
• Episodic airflow obstruction that is reversible
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PFT Patterns
• Asthmatics often have normal PFTs between attacks
• Diagnosis then requires a provocation test
– Usually methacholine challenge
– 20% fall in FEV1 with low dose methacholine
suggests AHR
Methacholine Challenge
• A positive test is diagnostic is a characteristic feature of asthma but can also be present in other conditions
• A negative test rules out asthma The Asthma Attack
• Typical asthma attack
has 2 phases
Acute phase (mins) (bronchoconstriction)
Late phase (hrs)
(edema and mucus hypersecretion)
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Clinical changes during an asthma attack
ABGs
• Hypoxemia with hypocapnia
• Hypoxemia (V/Q mismatch) responds to low flow oxygen
• Increased A‐a gradient
• Respiratory alkalosis is expected
• ABGs that look normal during an acute asthma attack signal respiratory muscle fatigue
Asthma is Chronic Inflammation
• Once asthma begins there is a perpetual situation of chronic inflammation
• An overt attack is a signal that the underlying inflammation has reached a critical threshold and is poorly controlled
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Asthma is Chronic Inflammation
• The number of clinical events in a specific time period and the PEFR are used to classify the intensity of the asthmatic inflammation
– Days/week
– Nights/month
– Variation in daily PEFR
Peak Expiratory Flow
• PEF‐ part of the FEV1
• Normal 600‐800 LPM
• Usually less than 20% difference between morning and night time values
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Asthma PEFR and FEV1
• Reasonable correlation between FEV1 and PEFR
• PEFR can be used in clinical situations to give an objective measurement of severity of airflow obstruction
Peak Flow Meter
• Easily measured
• Inexpensive
• Exaggeration of the normal diurnal difference also indicates increased airway inflammation
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Expert Panel Report 3
• Severity: frequency and intensity of symptoms and functional limitations the patient is experiencing currently or has recently experienced
• The number of clinical events in a specific time period and the PEFR are used to classify the intensity of the asthmatic inflammation
– Days/week
– Nights/month
– Variation in daily PEFR
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Expert Panel Report 3
• Control: frequency and intensity of symptoms and functional limitations the patient is experiencing currently or has recently experienced under treatment
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Expert Panel Report 3
• Before making a step up in therapy: – Assess patient adherence to medication – Inhaler technique*
– Environmental control measures – Consider comorbid disease
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Expert Panel Report 3
• Recommend inactivated influenza vaccination
• Consider pneumovax Expert Panel Report 3
• Risk: the likelihood of either asthma exacerbations, progressive decline in lung function or risk of adverse effects from medication
Assess Risk
Classification of asthma severity in patients who have severe asthma exacerbations
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• Because asthma is a chronic inflammatory disorder, persistent asthma is most effectively controlled with daily long‐term control medication directed toward suppressing inflammation.
• ICSs are the most consistently effective anti‐
inflammatory therapy for all age groups, at all steps of care for persistent asthma. Expert Panel Report 3
• Adding LABA to low‐dose ICS reduces the frequency of exacerbations to a greater extent than doubling the dose of ICS • Adding LABA has the potential risk of rare life‐
threatening or fatal exacerbations 17
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Combination therapy
• The addition of a long‐acting beta2 agonist to an inhaled corticosteroid is superior to all other combinations as well as to higher dosages of inhaled corticosteroids alone. • Combination therapy with an inhaled corticosteroid and a long‐acting beta2 agonist is the preferred treatment for adults and children with moderate to severe asthma
Expert Panel Report 3
• Omalizumab is recommended for consideration for youths ≥12 years of age who have allergies or for adults who require step 5 or 6 care (severe asthma). – Clinicians who administer omalizumab should be prepared and equipped to identify and treat anaphylaxis that may occur. Expert Panel Report 3
• Environmental control to reduce exposures
• Consideration of subcutaneous immunotherapy for patients who have allergies and require care at steps 2 to 4 when there is a clear relationship between symptoms and exposure to an allergen to which the patient is sensitive. 18
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Expert Panel Report 3
• Integrate asthma self‐management education
into all aspects of asthma care
• Provide to all patients a written asthma action plan that includes instructions for both daily management and actions to manage worsening asthma Occupational Asthma
• Constitutes 15% of all asthma
• Up to 30% of new‐onset adult asthma • One out of every 7 to 10 cases of adult
asthma is caused by workplace exposures. Occupational Asthma
• New‐onset asthma
• Symptoms worse at work or at night on workdays • Symptoms worse with specific exposures • Improved symptoms on vacation, over weekends, or other times away from work
• Presence of work‐related rhinitis or conjunctivitis
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Occupational Asthma
• The most practical approach is to document work‐
related changes in pulmonary function • Serial peak flow recordings are most frequently used and the most easily accessible test • The currently recommended method is for the patient to record his or her peak flow at least four times daily (on awakening, middle of work shift or lunch, end of work shift, and before bed) Asthma/Special situations
Allergic Bronchopulmonary Aspergillosis
(ABPA)
• ABPA involves growth of the fungus within mucus plugs in asthma patients
• Usually presents as refractory asthma responding only to oral corticosteroids with recurrent pulmonary infiltrates
Allergic Bronchopulmonary Aspergillosis
Diagnostic criteria: major and minor
• Asthma
• Elevated total IgE level >417 IU (1000 ng/mL)
• Eosinophilia > 5% • Positive immediate skin test (prick test)**
• Central bronchiectasis 20
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ABPA
• Treatment is prednisone, initially 0.5 mg per kilogram with gradual tapering • Azole antifungal agents as adjunctive therapy may also be helpful
• End‐stage ABPA often involves lung fibrosis
Asthma and Pregnancy
• The most common medical condition to complicate pregnancy
• 1/3 better, 1/3 same, 1/3 worse
• Episodes requiring emergency department visits or hospitalization have been reported in 9–11% of pregnant women managed by asthma specialists Asthma and Pregnancy Poorly managed asthma during pregnancy is associated with a higher risk of:
• preterm delivery
• low birth weight
• complications such as preeclampsia
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Asthma and Pregnancy
• The principles of management of asthma during pregnancy are not different from those recommended for nonpregnant women • Asthma attack carries more risk to fetus than use of asthma medications
Vocal cord dysfunction
• Vocal cord dysfunction can mimic asthma, but it is a distinct disorder. • Asthma medications typically do little, if anything, to relieve VCD symptoms. Variable flattening of the inspiratory flow loop on spirometry is strongly suggestive of VCD. • Diagnosis of VCD is from indirect or direct vocal cord visualization during an episode, during which the abnormal adduction can be documented. • VCD should be considered in patients with difficult‐
to‐treat, atypical asthma
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Chronic Obstructive Lung Diseases
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COPD
• COPD should be suspected in persons presenting with cough, dyspnea, or increased sputum production, especially those with a history of smoking • GOLD Stage 0 – At risk
COPD
Spirometry should be performed in patients 45 years or older who smoke and have a persistent cough • Identify the at risk population
• Diagnosis and stage COPD • Plan therapy
COPD
• Cigarette smoking is the most important risk factor
• Accounts for 80% to 90% of the risk
• About 15–30% of smokers develop COPD 25
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Asymptomatic smokers
– Health assessment‐ “know your flow”‐
– FEV1‐Decrease 30mL/ yr is normal – 50‐80 ml/yr in susceptible smokers COPD
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Smoking cessation
• The most important (and cost‐effective) intervention
• The only intervention able to reduce the progression of COPD
– patients who quit smoking experience less respiratory symptoms and hyper‐responsiveness than those who continue to smoke
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Smoking cessation
• The largest improvements in lung function and symptoms occur within the first year after cessation
• The rate of decline in lung function is slower among persons who quit smoking
• 10 years after quitting: The lung cancer death rate is about half that of a continuing smoker's
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Smoking cessation
• With good smoking cessation programs, 20 to 40 percent of participants are able to quit for at least one year
• Brief clinical interventions by health care providers can increase the chances of successful cessation, as can counseling and behavioral cessation therapies
• The use of a pharmaceutical product in concert with counseling doubles a person's chances of success 29
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Pharmacotherapy
Gross N. J. Mayo Clin Proc. 2008;83:1241-1250
© 2008 Mayo Foundation for Medical Education and Research
Theophylline
• A methylxanthine (theophylline) could be used in addition to these treatments or as an alternative in patients intolerant of β2‐agonist adverse effects
• Mechanism for improvement is not solely bronchodilation from phosphodiesterase inhibition
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Theophylline
• The doses currently recommended (approximately 300 mg once daily at bedtime or 200 mg every 12 hours) are unlikely to carry a risk of toxicity. • Narrow therapeutic range/toxicity • 8‐13 mcg/ml
• > 20 mcg/ml considered toxic level
• Monitoring blood levels at low dosages (plasma concentrations of 5‐10 mg/L) is not necessary.
Theophylline
Decreases level
• Rifampin
• Dilantin
• Phenobarbital
• Carbamazepine
• Smoking
Increases level
• Acyclovir
• Cimetidine*
• Macrolides
• Fluoroquinolones
• Propranolol*
• Allopurinol
• Zafirlukast
Theophylline
• Theophylline use may decrease serum levels of:
– Lithium
– Phenytoin 31
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COPD
• Common side effects of roflumilast include diarrhea, weight loss, nausea, headache, backache, decreased appetite, dizziness, and occasionally neuropsychiatric symptoms such as depression and suicidality. • Roflumilast is expensive and should be considered as add‐on therapy in highly selected patients. (only chronic bronchitis)
COPD
• Roflumilast is an oral phosphodiesterase‐4 inhibitor recently approved for use in patients with severe and very severe COPD associated with chronic bronchitis and a history of frequent exacerbations. COPD Treatment
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COPD
• None of the existing medications for COPD have yet been shown prospectively to modify the long‐term decline in lung function • Pharmacotherapy is used to decrease symptoms and reduce complications such as acute exacerbations Emphysema
• Emphysema is the permanent enlargement of the airspace distal to the terminal bronchioles with destruction of the alveolar septa • Destruction is due to imbalance between proteases and antiproteases
– Increased protease activity
• proteolytic elastase from neutrophils (tobacco smoke)
– Decreased antiprotease
• Alpha‐1‐antitrypsin deficiency
COPD
• 3‐5% of Emphysema is genetic
• Due to a severe hereditary deficiency of alpha1‐antitrypsin
• Most common in Caucasians – 96% of AAT deficiency patients have a ZZ genotype
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Emphysema
Panacinar
• 3%‐5% of emphysema from alpha‐1 deficiency
• Smoking exacerbates emphysema formation in A1A deficiency
• Alpha‐1‐antitrypsin deficiency: bullae in the lung bases rather than apices
• Onset in late 30’s rather than late 40’s
COPD • GOLD recommends α1‐antitrypsin screening in white patients who develop COPD before the age of 45 years or in those with a strong family history of COPD
Pulmonary rehabilitation
• All patients with COPD benefit from exercise training programs (pulmonary rehabilitation) • Reduces dyspnea, anxiety and depression, improves exercise capacity and quality of life • May reduce hospitalizations
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COPD
• Current recommendations recommend pulmonary rehabilitation for patients with symptomatic COPD who have an FEV1 less than 50%
Pulmonary rehabilitation
• Does not change Pulmonary function measurements • Does not change ABGs
• Does not decrease mortality
Oxygen
• Long‐term oxygen administration (>15 h per day) has been shown to improve survival in patients with chronic respiratory failure • It is the only therapy that increases their life span
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Chronic O2 use in COPD • Criteria for chronic (continuous) O2 use:
• Resting PaO2 < 55 or O2 sat < 88%
• PaO2 < 59 mmHg or Sat 89% with evidence of cor pulmonale or erythrocytosis (hct > 55%)
• Patients who qualify as above should be on oxygen 24 hours a day
Chronic O2 use in COPD
• Some patients desaturate with exercise or while sleeping • Survival benefit is unproven
• If prescribe supplemental O2 in the hospital you should re‐evaluate the continued need after 2 months
– Rule of 21
COPD
• Lung volume reduction surgery is an extensive surgical procedure in which parts of the lung are resected, leading to reduction of hyperinflation, improvement of mechanical efficiency of respiratory muscles, and improvement of expiratory flow rate
• It is recommended only in highly selected patients with COPD. 36
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Lung Volume Reduction Surgery
• LVRS should be considered in patients with severe COPD on maximal medical therapy who have completed pulmonary rehabilitation and meet the following criteria: – presence of homogeneous bilateral emphysema on CT scan
– postbronchodilator total lung capacity greater than 150% and residual volume greater than 100% of predicted
– maximum FEV1 no greater than 45% of predicted
– arterial PCO2 no more than 60 mm Hg and arterial PO2 of at least 45 mm Hg breathing ambient air. Lung Transplantation
• Patients with homogenous emphysema, an FEV1 not greater than 20% of predicted, and DLCO not greater than 20% of predicted have a median survival of 3 years and should be considered for lung transplantation
• This patient is a candidate for transplantation • Functional capacity and quality of life are improved after lung transplantation, but the effect on overall survival is mixed
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Bronchiectasis
• Persistent pathologic dilatation of the bronchi due to breakdown of smaller bronchial walls
• History of cough and foul smelling sputum
• Infection is a major cause (think necrotizing gram negative)
Bronchiectasis
• ABPA ‐ upper/central lung fields
• Cystic fibrosis • Immotile cilia syndromes: – Kartagener syndrome‐situs inversus
• Hypogammaglobulinemia: – consider with multiple sino‐pulmonary infections ‐ check IgA, IgG2, IgG4
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Bronchiectasis
• Diagnosed with high resolution computerized tomography (HRCT)
• Bronchogram
– if surgery considered for severe hemoptysis
Cystic fibrosis
• About 1,000 new cases each year • 70% are diagnosed by age 2 • 4% are not diagnosed until older than 18 yrs
– typical age at adult diagnosis 26yrs
Cystic Fibrosis
• Chronic unexplained pulmonary symptoms
– Less severe than childhood form
– Often misdiagnosed
• Usually infected – Pseudomonas, especially mucoid strains
– Staph spec.
– Burkholderia cepacia
• Sweat chloride > 60 mMol
– Genetic screening CFTR F508
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Cystic Fibrosis
• 40% of the CF patient population is age 18 or older
• Expected median survival of childhood CF is now 38 yrs
• Complications
–
–
–
–
Bronchiectasis
Hemoptysis
Pneumothorax
Infections
• ABPA
• Mycobacterium avium intracellulare
Cystic Fibrosis
• Usually treated in specialized centers
– Inhaled DNase for improving mucociliary clearance.
– Inhaled tobramycin as maintenance therapy
– Transplant: bilat, +/‐ heart — 50% 3 yr survival
Interstitial Lung Diseases
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Interstitial Lung Disease
• A stimulus causes inflammation (alveolitis) which if chronic results in irreversible healing by either fibrosis or granuloma formation
Interstitial Lung Disease
• The parenchymal healing involves the deposition of abnormal collagen and fibrosis
• The lung becomes “stiffer” and its expansion is “restricted”
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Interstitial Lung Disease
Exertional dyspnea or cough
Diffuse radiographic disease on CXR
Restrictive pulmonary function
Abnormal gas exchange parameters
• Abnormal high resolution CT of chest
•
•
•
•
ILD ‐ Dyspnea
• PaO2 decreases with exercise in early disease – a decreased DLCO
–  A‐a gradient
• Patient experiences dyspnea on exertion as first symptom
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ILD ‐ Dyspnea
• Desaturation during the 6 minute walk test at presentation is a stronger prognostic determinant in ILD than resting lung function
• An abnormal alveolar‐arteriolar PO2 difference that widens during exercise
DLCO
• Carbon monoxide transfer factor (DLCO) levels at presentation are a more reliable guide to outcome than other resting lung function variables • A DLCO level of less than 40% is indicative of advanced disease in fibrotic idiopathic interstitial pneumonia (IIP). ILD ‐ CXR
• Diffuse bilateral pulmonary infiltrates result from parenchymal scarring
• Characteristic CXR patterns often suggest etiology
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Late Symptoms
•
•
•
•
Progressive hypoxemia at rest
Dry, nonproductive cough
Pulmonary hypertension
Weight loss, malaise and fatigue may be noted
• Fever is rare and should suggest another dx
Physical Examination
• Crackles/dry rales (velcro) in 80%
– Most prevalent in the bases
• Clubbing present in 25‐50%
• Cor pulmonale with accentuated P2 in late phase
• Peripheral edema due to cor pulmonale
HRCT
• The diagnostic sensitivity of HRCT for ILD is 94% compared with 80% for chest radiography
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HRCT
• Ground glass opacity on HRCT scans predicts the response to treatment and increased survival compared with patients in whom the predominant HRCT abnormality is a reticular pattern
– Ground glass opacity = alveolitis
– >25% suggests treatment may be helpful ILD
• The combined information from clinical, laboratory and HRCT findings allows a correct diagnosis to be made in the majority of patients with ILD • Most will not need open lung biopsy
ILD
• 130 causes of ILD
• Consult ‐
• Physical findings of collagen vascular dz
• History of exposure
• Imaging ‐ Radiograph pattern
• Laboratory clues
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ILD
Inquiries should be made about: • Raynaud's phenomenon
• Skin thickening
• Dysphagia and acid reflux
• Arthralgia
• Rashes
• Ocular symptoms
• Sicca symptoms (dry eyes and mouth)
• Myalgia and proximal muscle weakness Acute Hypersensitivity Pneumonitis ‐
• History of recurrent ‘pneumonias’
• Temporal relation to organic trigger
• Serum precipitins are nonspecific and represent exposure, not necessarily disease.
• No eosinophilia (distinguish from eosinophilic pneumonia)
– Type III and Type IV reactions
Acute HP
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ILD ‐ HP
Farmer's lung
Moldy hay
Micropolyspora faeni
Bagassosis
Moldy sugar cane
Thermoactinomyces
sacchari
Grain handler's
lung
Moldy grain
Thermoactinomyces
vulgaris
Humidifier/airconditioner lung
Contaminated
heated water
T vulgaris
Bird breeder's lung Pigeons,
parakeets
Avian or animal
proteins
Byssinosis
Gram negative
endotoxin
Cotton fiber
Hypersensitivity Pneumonitis
• Mainstay of treatment is antigen avoidance
• Steroids for severe attacks
HP natural history ‐ untreated
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Pneumoconiosis
• Inhalation of inorganic stimulus
Know
• Asbestos – characteristic CXR
• Silica – characteristic CXR
• Coal – History of exposure
• Beryllium – exposure and CXR
Sarcoidosis
• Lofgren’s syndrome:
– Fever, arthralgias, erythema nodosum
– Usually means quick remission
• Heerfordt’s syndrome:
– Salivary gland involvement, uveoparotid fever
Sarcoidosis
• No consensus on many aspects of treatment
• Remember spontaneous remission is expected in most Stage I and Stage II patients
– 75% recover without treatment – 10‐20% progress to further stages
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Sarcoidosis
• Corticosteroids are used :
– Progressive or severely symptomatic – Uveitis
– Neurosarcoidosis
– Cardiac or spleen involvement
– Hypercalcemia, hypercalciuria
(Methotrexate is an alternative)
ILD ‐ Connective Tissue Diseases
All connective tissue diseases can result in pulmonary fibrosis and ILD
• Rheumatoid arthritis
• SLE
• Scleroderma*
• Sjogren’s (lymphocytic interstitial pneumonitis)
• Dematomyositis/polymyositis
Scleroderma Lung
• Diffuse pulmonary fibrosis in 80%
• Pulmonary involvement more severe in – Diffuse systemic slerosis
– Less so in the CREST variant
• Pulmonary hypertension*
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Scleroderma
• A subset of patients with SSc develop rapidly progressive ILD during the first 2 years of their disease • Spirometry and diffusion testing should be considered mandatory at the time of diagnosis • Patients with systemic sclerosis should have annual lung function testing early in disease Scleroderma
• Patients with declining DLCO or DLCO <50% predicted should have transthoracic echocardiography performed • Long‐term warfarin therapy should be prescribed in patients with CTD‐associated pulmonary artery hypertension CTD ‐associated ILD
• For the majority of CTD, with the exception of systemic sclerosis (SSc), recommended initial treatment for ILD is oral prednisolone at an initial dose of 0.5–1 mg/kg • High‐dose corticosteroid treatment (daily prednisolone dose >10 mg) should be avoided if at all possible in scleroderma because of the risk of renal crisis
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Drugs
• Nitrofurantoin • Methotrexate •
•
•
•
Bleomycin Mitomycin C Amiodarone*
Beta blockers
Idiopathic Pulmonary Fibrosis
• IPF accounts for 40‐50% of ILD but remains a diagnosis of exclusion
• Unidentified autoimmune trigger
• Age 40‐70, equal gender involvement
• No extrapulmonary manifestations (except clubbing)
IPF – Diagnosis HRCT
• Diagnosis can be made 90% of time by trained radiologists
– Patchy, peripheral, subpleural, bibasilar reticular pattern with ground glass opacities.
– Traction bronchiectasis and bronchiolectasis +/‐
subpleural honeycombing may be present
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Typical Clinical or HRCT Findings Absent
• Via open thoracotomy or VATS
– Is specifically helpful if atypical radiologic findings are present – Rarely establishes etiology of ILD
• Transbronchial biopsy, TBB
– may be helpful in dx other disease that mimics IPF but not for IPF itself
– Not helpful in assessing degree of fibrosis or inflammation
IPF ‐ Disease Course
• Progresses in a relentless and insidious manner
• Spontaneous remissions do not occur
• Mean survival from time of dx is 2‐4 years with a 5 year survival of 30‐50%.
IPF ‐ Disease Course
•
•
•
•
Respiratory failure (40%)
Heart failure and ischemic heart disease
Pulmonary embolism
Lung cancer – The incidence of bronchogenic carcinoma is increased
– Occurs in 10‐15% of advanced IPF
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IPF ‐ Treatment
• 2 new drugs: pirfenidone and nintedanib
• No pharmacologic therapy proved to be beneficial
– Corticosteroids
– Azathioprine
– Cyclophosphamide
– MTX or chlorambucil
– Interferon gamma
IPF ‐ Treatment
Response rate to therapy steroids, cytotoxic/immunosuppressive is higher when significant ground‐glass opacities and no honeycombing noted on HRCT •
Extensive honeycomb changes or reticulation and no or minimal ground‐glass opacities suggest a low likelihood of response to medical therapy and higher mortality
ILD – Treatment response
• Radiographic improvement rare
• Objective improvement in 20‐30%
• Objective improvement is needed to continue therapy
–  10‐15% in FVC, DLCO, exercise O2 sat
– ABIM: A‐a gradient response to exercise
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Pulmonary Hypertension
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Primary Pulmonary Hypertension
Predominantly in young women
Ages 20‐40 years
Unknown cause
Rare ‐ 500‐1000 new cases/yr USA
Exertional dyspnea, fatigue, syncope and chest pain • Sporadic or Familial
•
•
•
•
•
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Primary Pulmonary Hypertension
Right Heart Catheterization: •
•
•
•
Increased RA and right side pressures. Increased pulmonary vascular resistance PADP usually > 20 mm Hg
Mean PAP > 25 mm Hg at rest
• PCWP is normal
• There can be no co‐existent cardiopulmonary disease for accurate diagnosis
Primary Pulmonary Hypertension
• Trial of vasodilators only during right heart cath since hemodynamic collapse can occur
• Responders first get Calcium Channel Blockers (25%)
– the primary treatment modality, and titration to high doses appears to slow the progression of the disease
Primary Pulmonary Hypertension
• Non repsonders to CCB:
– Prostacyclin by IV infusion pump, nasal, oral
• Concerns are complications and tachyphylaxis
– Bosentan ‐ an oral endothelin
receptor antagonist • Concerns are hepatic insufficiency Monitor LFT’s monthly
– Sildenafil and others • Heart‐lung transplantation
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Pulmonary Thromboembolism
Calf Thrombi
• The majority of thrombi below the popliteal vein (calf thrombi) will spontaneously resolve (80%) and do not embolize to the lung
• 20% will propagate to the thigh
• Asymptomatic calf thrombi are followed with serial imaging studies not anticoagualtion
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Pathophysiology
• Approximately half of patients with proximal DVT (50%) develop pulmonary embolism
• Anticoagulation is indicated An Observation
• The death rate has not changed in the past 30 years
• Once diagnosed and treatment is started death from PE is uncommon
– Effective therapy reduces mortality to 2‐8%
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Risk Factors
• At least, one recognizable risk factor present in nearly 80% of patients with PE
• No immediately recognizable risk factor in 20%, i.e., “Idiopathic PE”
Risk Factors
• The most important risk factor for ‘Idiopathic PE’ is inherited or acquired hypercoagulability
• Antithrombin III deficiency, protein C deficiency, and protein S deficiency are uncommon in the general population • They are also infrequent in patients with VTE (2 to 5%) 60
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Newly Recognized Risk Factors
Risk Factors
• Homocysteinemia
The five more recently • Prothrombin gene discovered mutation
hypercoagulable states •
Factor V Leiden are far more frequent in (heterozygous)
the general population
• Factor V Leiden
(homozygous)
• Increased factor VIII
Idiopathic VTE
• Factor V Leiden mutation present in 40% of cases
• Increased factor VIII in 11%
• Also suspect hypercoaguability from occult malignancy
– pancreas and prostate, breast, lung, uterine, brain
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Pulmonary Embolism
PTE can present as three different syndromes:
• Pulmonary infarction
• Acute cor pulmonale
• Acute unexplained dyspnea
Acute unexplained dyspnea
• Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors.
• Ann Intern Med. 2006 Mar 21;144(6):390‐6.
• CONCLUSION: This study showed a 25% prevalence of PE in patients with COPD hospitalized for severe exacerbation of unknown origin
Clinical Manifestations
• Clinical signs and symptoms are nonspecific • Objective testing is always necessary
• Interpretation of tests is improved when pretest probability of PTE is assessed
– Geneva score
– Wells score
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D‐Dimer
Very sensitive in excluding a diagnosis of PE in the setting of:
– Normal values, i.e., less than 500 ng/ml and
– Low clinical suspicion
PTE
• D‐dimer testing is very sensitive for the detection of thromboembolic disease; in patients with a low probability for deep venous thrombosis or PE, a negative study is helpful in excluding the need for further testing. • However, D‐dimer testing is less helpful in patients with an intermediate to high probability of disease, which is an indication for definitive testing; D‐dimer testing should not be obtained in these situations.
Spiral CT
• CT angiogram is recommended by most PIOPED II investigators as the first imaging test
PIOPED II Investigators. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354:2317‐2327.
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V/Q Scan – 3 readings
• High clinical probability and high probability scan has a 96% positive predictive value ‐ treat
• Normal scan has 97% negative predictive value –
look for another cause
• Indeterminate – do another test
Echocardiography
• Low sensitivity for diagnosing PE
• Has been used in cases of massive pulmonary embolism to justify the use of thrombolytics
–  Troponin
–  BNP
Treatment needed • Helical CT: intraluminal filling defect in a lobar or main pulmonary artery • US for DVT: evidence of acute DVT
• V/Q scan: high‐probability reading
• Pulmonary angiography: intraluminal filling defect
• Echocardiogram: ‘Thrombus‐in‐Transit”
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Anticoagulation
• Mainstay for stable patient is fractionated heparin
– Bolus 5000 to 10,000 units
– Drip of @ 30,000 units/24 hours
– PTT 1.5 to 2.5
• LMWH also useful with no difference in recurrence of thromboembolism, bleeding episodes or mortality
Anticoagulation
• Warfarin should be started within 3 days of initial heparin therapy
• Overlap with heparin until INR is 2.0 to 3.0 for at least 2 days
• Continue for 3‐6 months
• Longer if risk factor persists
Thrombolytic Therapy
• Results in more rapid clot resolution than heparin, but at 5 days both treatments produce similar improvements in pulmonary perfusion
• In hemodynamically stable patients, thrombolysis has not been proven to reduce mortality or risk of recurrent PTE
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Thrombolytic Therapy
• Reduces mortality in patients with hemodynamic instability or shock due to massive PTE
• Role is limited to patients with PTE and hemodynamic instability
IVC Filter
• If anticoagulant therapy is contraindicated
• When adequate anticoagulation has failed to prevent recurrent embolism
• When thrombolytics are contraindicated in an unstable patient that could not tolerate an additional episode (short term retrievable filter)
Surgical Embolectomy
• Open operation
• Percutaneous catheter techniques
• Surgical embolectomy limited to hemodynamically unstable patient who cannot receive thrombolysis
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Prevention
• Currently available methods of prophylaxis reduce the incidence of venous thromboembolism by about 2/3
• Several studies have shown that prophylaxis is underused, even in patients with obvious risk factors
Pregnancy and PE
• Pregnancy is an independent risk factor for thromboembolism • The incidence of DVT is five times higher in pregnant women than nonpregnant women • The potential morbidity of pulmonary embolism and the risk of anticoagulant therapy necessitate definitive diagnosis Pregnancy and PE
Managed similarly to nonpregnant patients, with the following modifications. • Ultrasonography is performed as an initial test
• V/Q scanning ‐the amount of radioisotope used for the perfusion scan can be reduced and the duration of scanning extended
• Spiral CT – can be performed with shielding
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Pregnancy and PE
• Use of warfarin during pregnancy is contraindicated • It crosses the placenta and is teratogenic. PTE
• Subcutaneous administration of unfractionated heparin, low‐molecular‐weight heparins, and fondaparinux are all safe and effective for the treatment of acute pulmonary embolism. • A recent clinical trial showed that high‐dose subcutaneous unfractionated heparin, administered without dose adjustment guided by the activated partial thromboplastin time, was as safe and effective as low‐molecular‐weight heparin administered in the same fashion.
PTE
• Unfractionated heparin does not rely on normal renal function for clearance and would be an appropriate option in this patient.
• Low‐molecular‐weight heparins are renally cleared and would accumulate unpredictably in this patient with acutely worsening renal function.
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PTE
• Results of a D‐dimer assay performed after a period of anticoagulation therapy have been shown to be predictive of thrombotic recurrence. • The assay must be done 3 to 4 weeks after warfarin therapy is stopped. An elevated high‐sensitivity D‐dimer assay result predicts an increased risk for recurrence by at least fourfold compared with a normal result. • Thus, a positive assay provides further impetus to continue long‐term anticoagulation, whereas a normal assay might lead to cessation of therapy because of an altered risk/benefit ratio for continued anticoagulation. Who Should Be Tested?
Select testing should be considered mainly in the following circumstances:
– Idiopathic (i.e., spontaneous) VTE
– VTE at young age (<45 years)
– Recurrent VTE
– VTE in unusual sites VTE in the setting of a strong family history of VTE
– Recurrent pregnancy loss (more than three consecutive first‐trimester pregnancy losses without an intercurrent
term pregnancy)
Pleural Effusions
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20% solution
• The cause of effusion is below the diaphragm 20% of the time
• CHF causes unilateral left effusion only 20% of the time
• Transudates are misclassified as exudates 20% of the time
• After a good work‐up, 20% remain unexplained
• About 20% of these will be cancer
Transudative Effusions
• If a pleural fluid is a transudate then it can be attributed to an imbalance of hydrostatic forces
• No further investigative procedures need to be done
Transudative Effusions
• The most common causes are:
– CHF (500,000/yr)
– Cirrhosis (50,000/yr)
– Nephrosis
– Hypoalbuminemia
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Exudative Pleural Effusion
• An exudate is suggested if one of the following is present:
– pleural/serum protein > 0.5
– pleural/serum LDH > 0.6
– Absolute LDH value > 2/3 normal value for serum, usually > 200 IU
– Correct classification 80% of the time
Exudative Pleural Effusion
• 20% of the time a transudate may look like an exudate by LDH or protein criteria
• If a transudate then:
– Pleural cholesterol less than 45
– If the difference between the albumin level in the blood and the pleural fluid is greater than 1.2 g/dL
Exudative Effusions
• The most common causes are:
– Bacterial pneumonia (300,000/yr)
– Malignancy (200,000/yr)
– Pulmonary embolism (75,000/yr)
– Tuberculosis
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Parapneumonic Effusion
• The most common exudative pleural effusion in the USA is associated with bacterial
pneumonia
• An analysis of the fluid is required to determine if antibiotic therapy will be sufficient or if the fluid needs to be drained
Parapneumonic effusion
• Considered uncomplicated when:
– There is no pus in the pleural space
– Organisms are not present on Gram’s stain or culture
– pH >7.2
• Antibiotics alone will do the job
Malignant Effusion
• Generally large > 50% hemithorax
• Quick to reaccumulate
• Generally lymphocytic WBC’s
• Often bloody
– 3 “T’s” = tumor, trauma, thromboembolism
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Exudative Effusions: Cytology
• 1st sample 60% yield • Three separate samples = 90% yield
• Yield not significantly increased by blind needle biopsy!
– Cope
– Abrams
Tuberculous Effusion
• AFB recovered in only 10%, but yield can be increased with up to 3 taps
• Culture for AFB is positive in 65%
• Pleural biopsy and culture together identify 85% • Blind pleural biopsy may be helpful
Pleural Biopsy
• Pleural needle biopsy is most useful for diagnosing granulomatous disease (TB)
• Yield for three biopsies samples:
• TB 80% (compared to 50% Ca)
– shows caseating granuloma
– If sent for culture TB yield increases
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Tuberculous Effusion
• Adenosine deaminase levels may be helpful
– Levels > 50 U/L 94% sensitive & 90% specific
– Levels < 45 U/L 100% sensitive and specific for nontuberculous etiology
• Mesothelial cells are rarely present
Sleep Disordered Breathing
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OSA Tracing
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Sleep Disordered Breathing
• Snoring, apnea, restlessness sleep, daytime somnolence, cognitive impairment
• Apnea is cessation of airflow for at least ten seconds
• Sleep apnea syndrome: >10 apneic spells an hour during sleep study
Polysomnography
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Sleep Apnea
• Obstructive ‐ continued respiratory effort during the absence of airflow
• Central ‐ absence of effort and airflow
OSA
• More than 15‐20/hr requires treatment
• Treatment of OSA:
– Weight loss for mild – Nasal CPAP or BiPAP for moderate/severe
Treatment of OSA
• Weight loss
• Avoid sedatives, ETOH
• Nasal CPAP/BiPAP‐ splints the pharynx
• Severe: tracheostomy
• Uvulopalatopharyngoplasty eliminates snoring but only 50% effective at relieving sleep apnea
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Central Sleep Apnea
• Transient loss of ventilatory drive during sleep. May act like OSA with arousals etc.
• Disruption in central ventilatory drive or neuromuscular control of respiratory muscles
• Treatment: acidification with acetazolamide, supplemental O2, CPAP
Narcolepsy
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•
•
•
Severe daytime hypersomnolence
Cataplexy
Sleep paralysis
Hallucinations when drowsy
• Polysomnography and Multiple Sleep Latency Test (MSLT) checks hyper‐somnolence and frequency of rapid eye movement (REM)
• Treat: stimulants and REM suppression by tricyclic antidepressants and selective serotonin reuptake inhibitors
Restless Leg Syndrome
•
•
•
•
Paresthesias that improve with movement
Worse in the evening and at night
Can cause insomnia
Associated with periodic limb movement disorder ‐ contraction of the anterior tibialis muscle during sleep • Treat: dopaminergic agonists/narcotics
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