Tf6f2018
`
`Evalualion of the Pulmonary Patient - Pulmonary Disorders - Merck Manuals Professional Edition
`
`\\\ MERCK MANUAL
`
`Ei'lll'
`
`Professional ,e’ Pulmonary Disorders I Approach to the Pulmonary Patient
`
`Evaluation of the
`
`Pulmonary Patient
`
`By Noah Lechtzin, MD, MHS, Associate Professor of Medicine and
`Director, Adult Cystic Fibrosis Program. Johns Hopkins University
`School of Medicine
`
`Key components in the evaluation of patients with pulmonary symptoms are the history, physical
`
`examination, and, in most cases, a chest x-ray. These components establish the need for
`subsequent testing. which may include pulmonary function testing and A36 analysis, CT or other
`
`chest imaging tests. and bronchoscopy.
`
`History
`
`The history can often establish whether symptoms of dyspnea, chest pain, wheezing, stridor,
`hemoptysis, and cough are likely to be pulmonary in origin. When more than one symptom
`
`occurs concurrently. the history should focus on which symptom is primary and whether
`constitutional symptoms, such as fever, weight loss, and night sweats, are also present. Other
`important information includes
`
`Occupational and environmental exposures
`
`Family history, travel history, and contact history
`
`Previous illnesses
`
`Use of prescription. OTC. or illicit drugs
`
`Previous test results (eg, tuberculin skin test, chest x-rays)
`
`Physical Examination
`
`Physical examination starts with assessment of general appearance. Discomfort and anxiety,
`
`body habitus, and the effect of talking or movement on symptoms (eg, inability to speak full
`httpsriMw‘merckmanua|s.oomiproiessional!pulmonary-disorderstapproach-tothe-puImonary-patientievaIuation-oi-the~pulmonary~patient
`
`1!?
`
`WATSON LABORATORIES v. UNITED THERAPEUTICS, lPR2017-01621
`
`UNITED THERAPEUTICS, EX. 2113
`
`Page 1 of?
`
`

`

`

`

`?f6f2018
`
`Evaluafion of the Pulmonary Patient - Pulmonary Disorders - Merck Manuals Professional Edition
`
`distinguished from pathologic clubbing by the absence of pulmonary symptoms or disease and
`
`by the presence of clubbing from an early age (by patient report).
`
`
`
`Finger Clubbing
`
`© Springer Science+Business Media
`
`Measuring finger clubbing.
`
`The ratio of the anteroposterior diameter of the finger at the nail bed (aub) to that at the distal
`interphalangeal joint (c—d) is a simple measurement of finger clubbing. It can be obtained
`readily and reproducibly with calipers. If the ratio is > 1, clubbing is present. Finger clubbing is
`also characterized by loss ofthe normal angle at the nail bed.
`
`Giubbed linger
`
`Normal linger
`/ 150
`
`>130 \
`
`Chest wall deformities. such as pectus excavatum (a sternal depression usually beginning over
`
`the midportion of the manubrium and progressing inward through the xiphoid process) and
`kyphoscoliosis, may restrict respirations and exacerbate symptoms of preexisting pulmonary
`disease. These abnormalities can usually be observed during careful examination after the
`
`patient's shirt is removed. Inspection should also include an assessment of the abdomen and the
`
`extent of obesity. ascites, or other conditions that could affect abdominal compliance.
`
`Abnormal breathing patterns cause fluctuations in respiratory rate so respiratory rate should
`be assessed and counted for 1 min.
`
`httszMu-M.merckmanualsoomlprol'esslonallpulmonary-disorderslapprmmlome-puImonary-pet'lenUevaiuation-of-tne-pulmonary-patient
`
`3!?
`
`UNITED THERAPEUTICS, EX. 2113
`WATSON LABORATORIES v. UNITED THERAPEUTICS, lPR2017-01621
`
`Page 3 of 7
`
`

`

`?f6f2018
`
`Evaluation of the Pulmonary Patient - Pulmonary Disorders - Merck Manuals Professional Edition
`
`- Cheyne-Stokes respiration (periodic breathing) is a cyclic fluctuation of respiratory rate
`
`and depth. From periods of brief apnea, patients breathe progressively faster and deeper
`(hyperpnea), then slower and shallower until they become apneic and repeat the cycle.
`
`Cheyne-Stokes respiration is most often caused by heart failure, a neurologic disorder (eg,
`stroke, advanced dementia), or drugs. The pattern in heart failure has been attributed to
`delays in cerebral circulation; respiratory centers lag in recognition of systemic
`acidosis/hypoxia (causing hyperpnea) or alkalosisfhypocapnia (causing apnea).
`
`- Biot respiration is an uncommon variant of Cheyne-Stokes respiration in which irregular
`periods of apnea alternate with periods in which 4 or 5 deep. equal breaths are taken. it
`differs from Cheyne—Stokes respiration in that it is characterized by abrupt starts and stops
`and lacks periodicity. It results from injury to the CNS and occurs in such disorders as
`
`meningitis.
`
`- Kussmaul respirations are deep, regular respirations caused by metabolic acidosis.
`
`Pulmonary hypertension, sometimes observed during inspection, indicates an increase in right
`atrial and usually in right ventricular pressure. The elevated pressure is usually caused by left
`
`ventricular dysfunction, but it may also be due to a pulmonary disorder causing pulmonary
`
`hypertension. The presence ofjugular venous distension should prompt a search for other signs
`
`of cardiac disorder (eg, 3rd heart sound [53] gallop, dependent edema).
`
`Auscultation
`
`Auscultation is arguably the most important component of the physical examination. All fields of
`
`the chest should be listened to, including the flanks and the anterior chest, to detect
`abnormalities associated with each lobe of the lung. Features to listen for include
`
`0 Character and volume of breath sounds
`
`. Presence or absence of vocal sounds
`
`:- Pleural friction rubs
`
`0 Ratio of inspiration to expiration (l : E ratio)
`
`Cardiac auscultation may reveal signs of pulmonary hypertension, such as a loud pulmonic 2nd
`heart sound (P2), and of right heart failure, such as a right ventricular 4th heart sound (54) and
`
`tricuspid regurgitation.
`
`The character and volume of breath sounds are useful in identifying pulmonary disorders.
`Vesicular breath sounds are the normal sounds heard over most lung fields. Bronchial breath
`sounds are slightly louder, harsher, and higher pitched; they normally can be heard over the
`
`trachea and over areas of lung consolidation, such as occur with pneumonia.
`
`Typical breath sounds heard over most lung fields.
`
`https:le.merckrnanualsoorrvprol'esslonalrpulmonary-disordersiapproachntdthe-puImonary-petlenUevaiuation-of-the-pulmonary-patient
`
`4!?
`
`UNITED THERAPEUTICS, EX. 2113
`WATSON LABORATORIES v. UNITED THERAPEUTICS, IPR2017-O1621
`
`Page 4 of 7
`
`

`

`?.l6f2018
`
`Evalualion of the Pulmonary Patient - Pulmonary Disorders - Merck Manuals Professional Edition
`
`Normal Breath Sounds
`
`Audio file courtesy of David W. Cugell. MD.
`
`Typical breath sounds heard over the trachea and areas of lung consolidation.
`
`Normal Bronchial Breath Sounds
`
`Audio file courtesy of David W. Cugell, MD.
`
`Crackles
`
`Audio file courtesy of David W. Cugell. MD.
`
`Prolonged expiratory phase with wheezing.
`
`Wheezing
`
`Audio file courtesy of David W. Cugell, MD.
`
`Inspiratory stridor in croup.
`
`Stridor
`
`Audio file courtesy of David W. Cugell, MD.
`
`A leathery sound that fluctuates with the respiratory cycle.
`
`Friction Rub
`
`Audio file courtesy of David W. Cugell, MD.
`
`Areas of consolidation cause a patient‘s vocalized "E" to sound like ‘A.“
`
`E to A Change
`
`Audio file courtesy of David W. Cugell, MD.
`
`Adventitious sounds are abnormal sounds. such as crackles. rhonchi. wheezes. and stridor.
`
`httpvaw-w.merckrnanualsoormnrol'esslonalrwlmonary-«disorderslapproach-lothe-puImonary-petlenUevaluation-of-the-pulmonary-patient
`
`517
`
`UNITED THERAPEUTICS, EX. 2113
`WATSON LABORATORIES v. UNITED THERAPEUTICS, IPR2017-O1621
`
`Page 5 of 7
`
`

`

`”612018
`
`Evaluation Of the Pulmonary Patient - Pulmonary Disorders - Merck Manuals Professional Ed'fllOn
`
`Crackles (previously called rales) are discontinuous adventitious breath sounds. Fine
`
`crackles are short high-pitched sou nds; coarse crackles are longer—lasting low-pitched
`sounds. Crackles have been compared to the sound of crinkling plastic wrap and can be
`
`simulated by rubbing strands of hair together between 2 fingers near one's ear. They occur
`most commonly with atelectasis, alveolar filling processes (eg. pulmonary edema). and
`interstitial lung disease (eg. pulmonary fibrosis); they signify opening of collapsed ainrvays or
`alveoli.
`
`Rhonchi are low-pitched respiratory sounds that can be heard during inspiration or
`expiration. They occur in various conditions. including chronic bronchitis. The mechanism
`
`may relate to variations in obstruction as airways distend with inhalation and narrow with
`exhalation.
`
`Wheezes are whistling, musical breath sounds that are worse during expiration than
`inspiration. Wheezing can be a physical finding or a symptom and is usually associated with
`dyspnea.
`
`Stridor is a high-pitched. predominantly inspiratory sound formed by extrathoracic upper
`
`airway obstruction. It usually can be heard without a stethoscope. Stridor is usually louder
`
`than wheezing, is predominantly inspiratory, and is heard loudly over the larynx. It should
`
`trigger a concern for life-threatening upper airway obstruction.
`
`Decreased breath sounds signify poor air movement in airways, as occurs with asthma
`
`and COPD where bronchospasm or other mechanisms limit airflow. Breath sounds may
`also be decreased in the presence of a pleural effusion. pneumothorax, or obstructing
`endobronchial lesion.
`
`Vocal sounds involve auscultation while patients vocalize.
`
`Bronchophony and whispered pectoriloquy occur when the patient's spoken or
`
`whispered voice is clearly transmitted through the chest wall. Voice transmission results
`
`from alveolar consolidation. as occurs with pneumonia.
`
`Egophony (E to A change) is said to occur when. during auscultation. a patient says the
`letter ”E" and the examiner hears the |etter”A," again as occurs with pneumonia.
`
`Friction rubs are grating or creaking sounds that fluctuate with the respiratory cycle and sound
`like skin rubbing against wet leather. They are a sign of pleural inflammation and are heard in
`
`patients with pleuritis or empyema and after thoracotomy.
`
`|:E ratio is normally 1:2 but is prolonged to 2 1:3 when airflow is limited, such as in asthma and
`
`COPD, even in the absence of wheezing.
`
`Percussion and palpation
`
`Percussion is the primary physical maneuver used to detect the presence and level of pleural
`
`effusion. Finding areas of dullness during percussion signifies underlying fluid or, less commonly,
`httszMw-w.merokmanualsoornlprol'essionelipulmona ry-disordersia pproach-tothe-pulmona ry-petientlevaiuation-of-the-pulmona ry-pa tith
`
`5"?
`
`UNITED THERAPEUTICS, EX. 2113
`WATSON LABORATORIES v. UNITED THERAPEUTICS, IPR2017-01621
`
`Page 6 of 7
`
`

`

`7(62018
`
`Evaluallori of the Pulmonary Patient - Pulmonary Disorders - Merck Manuals Professional Edition
`
`consolidation.
`
`Palpation includes tactile fremitus (vibration of the chest wall felt while a patient is speaking); it is
`decreased in pleural effusion and pneumothorax and increased in pulmonary consolidation (eg,
`lobar pneumonias). Point tenderness on palpation may signal underlying rib fracture or pleural
`inflammation.
`
`In cor pulmonale, a right ventricular impulse at the left lower sternal border may become evident
`and may be increased in amplitude and duration (right ventricular heave).
`
`Last full reviewi’revision August 2016 by Noah Lechtzin, MD, MHS
`
`9 m
`
`it) 2018 Merck Sharp 3: Dohme Corp., a subsidiary of Merck 3. Co.. Inc., Kenilworth, NJ. USA
`
`hflszMmmerckma nu als‘convprofessionalrpulmona ry-disordersia pproach-lothe-pulmona ry-patienvevaluation d-the-pulmna ry-patient
`
`W7
`
`UNITED THERAPEUTICS, EX. 2113
`WATSON LABORATORIES v. UNITED THERAPEUTICS, |PR2017-01621
`
`Page 7 of T
`
`