Dyspnea R6.0

In 1963, Campbell and Howell wrote that dyspnoea was closely linked to structures in the CNS. They put forward the theory of "length-tension adaptation of the respiratory muscles" and thus offered an explanation for the occurrence of dyspnoea in both healthy people and those with the disease.

Nowadays, it is assumed that various mechanisms are important to varying degrees (Weingärtner 2004).

According to the American Thoracic Society, dyspnoea (from the Greek "dys" = heavy and "pnoia" = to breathe heavily - Kroegel 2014) is a subjective experience of breathing difficulties that can vary in intensity and consists of qualitatively different sensations (Kasper 2015). Dyspnoea is one of the most unpleasant sensations of all. Even under controlled laboratory conditions, test subjects report the feeling of impending death (Herigstad 2011).

Dyspnoea and pain have similarities: they are located in the same regions of the brain and are experienced subjectively. In terms of research, however, dyspnoea lags years behind pain research (Herigstad 2011).

Dyspnea is divided into:

• Nocturnal paroxysmal dyspnea:

This occurs approx. 2 - 5 h after the onset of sleep and is usually accompanied by coughing and sweating. It improves after sitting up or getting out of bed.

Nocturnal dyspnea usually occurs with interstitial pulmonary edema or, more rarely, with interalveolar pulmonary edema (Gerok 2007).

• Orthopnoea:

This occurs in particular when lying flat (Gerok 2007). It is often found in congestive heart failure (CHF), mechanical impairment of the diaphragm, e.g. in obesity, asthma (Kasper 2015).

• Orthodeoxia:

This involves a decrease in arterial oxygen saturation and the associated feeling of dyspnea when standing (Kroegel 2014).

• Platypnea:

Platypnea occurs in particular when the body is in an upright position. It is caused by abnormal ventilation-perfusion conditions, e.g. lack of diaphragm support, weakness of the abdominal muscles, etc. Platypnoea rarely occurs in pulmonary emphysema or congenital vitia (Gerok 2007).

• Speech dyspnea:

This is a restricted or interrupted flow of speech caused by tachypnoea (Kroegel 2014)

• Trepopnoea:

In trepopnea, there is shortness of breath when lying on the side, preferably the left side. It is typical of dyspnea as a result of cardiac disease (Gerok 2007).

Depending on the (presumed) localization, a distinction is made between inspiratory dyspnoea, which occurs in the upper airways, and expiratory dyspnoea, which occurs in the lower airways, particularly in the bronchi (Gerok 2007).

Depending on the time course of dyspnoea, a distinction is made between:

• acute dyspnoea due to e.g.:
  • aspiration
  • asthma attack
  • laryngeal edema
  • pulmonary embolism
  • pulmonary edema
  • Pneumothorax
  • VCD = vocal cord dysfunction (Herold 2020)
  • Myocardial infarction
  • Pericardial tamponade
  • cardiac arrhythmias
  • Psychogenic hyperventilation
  • anxiety (Weingärtner 2004)
• subacute dyspnea in e.g.:
  • pneumonia (Herold 2020)
• chronic dyspnoea: Defined by the American Thoracic Society 1999 as dyspnoea lasting > 1 month (Steffen 2008), which almost always manifests as exertional dyspnoea (Weingärtner 2004) in e.g.:
  • COPD
  • Emphysema (Herold 2020)
  • Parenchymal diseases of the lungs (Weingärtner 2004)
  • heart failure (Herold 2020)
  • coronary heart disease
  • valvular heart disease
  • cardiomyopathy
  • chronotropic incompetence
  • arterial hypertension
  • endocrine diseases
  • neuromuscular diseases
  • anemia (Weingärtner 2004)
• nocturnal dyspnea:
  • Nocturnal dyspnoea may occur with impaired left ventricular function as a result of increased pressure in the pulmonary capillaries (is characteristic but not pathognomonic [Weingärtner 2004])

According to the New York Heart Association, the severity of chronic dyspnoea can be divided into 4 degrees of severity depending on the exertion:

• NYHA I: no dyspnea under physiological conditions
• NYHA II: dyspnea during heavy exertion such as climbing stairs
• NYHA III: Dyspnoea with light exertion such as walking on level ground
• NYHA IV: Dyspnea at rest (Steffen 2008)

and according to the American Thoracic Association in:

• Grade 0: No shortness of breath when walking fast on level ground or slightly uphill
• Grade 1: mild dyspnea when walking fast on level ground or slightly uphill
• Grade 2: moderate shortness of breath, must walk slower than people of the same age group or even stop when walking fast on level ground
• Grade 3: severe shortness of breath occurs when walking on level ground after approx. 100 m or after a few minutes
• Grade 4: very severe breathlessness when dressing and undressing. The patient is no longer able to leave the house on foot (Steffen 2008).

and according to the modified Borg scale in:

• 0: not at all
• 0.5: very, very slight
• 1: very slight
• 2: mild
• 3: moderate
• 4: somewhat difficult
• 5: heavy
• 6:
• 7: very difficult
• 8:
• 9: very, very difficult
• 10: maximum (Steffen 2008)

and the VAS (Visual Analogue Scale):

Like the modified Borg scale, it is based on self-assessment. The patient uses a 100 mm scale to determine their subjectively perceived symptoms between "no shortness of breath" and "extreme shortness of breath" (Kroegel 2014).

Dyspnoea is one of the most common symptoms in both general practice and hospital emergency departments (Berliner 2016).

In emergency rooms, patients with dyspnea account for about 7%, in outpatient settings for about 25%, and in pulmonary practices for about 60% (Herold 2020).

In the 1987 Framingham study, up to 27% of patients complained of dyspnea. The symptomatology of patients with dyspnoea was up to two thirds due to a cardiopulmonary cause (Weingärtner 2004).

In patients with chronic dyspnea, seven entities are responsible for it in > 85 % of cases: bronchial asthma, COPD, heart failure, interstitial lung disease, coronary heart disease/ cardiac ischemia, pneumonia, psychogenic causes (Berliner 2016).

In the majority of cases, dyspnea is caused by deviations from the normal function of the cardiovascular and respiratory system (Kasper 2015). The causes are manifold:

• 1. pulmonary or thoracic causes:
  • Aspiration
  • Bronchial asthma
  • COPD
  • glottic edema
  • pulmonary embolism
  • pulmonary emphysema
  • pleural effusion
  • pneumonia
  • pneumothorax
  • Rib fractures
  • vocal cord dysfunction (VCD)
  • and other lung diseases (Herold 2020)
• 2. cardiac causes such as:
  • acute coronary syndrome
  • heart failure
  • cardiomyopathies
  • myocarditis
  • pericardial effusion
  • pericarditis
  • Pericardial tamponade
  • Vitia (Herold 2020)
• 3. extrathoracic causes such as:
  • Obesity
  • anemia
  • ascites
  • Emotional factors such as hyperventilation
  • Diseases of
    • nerves
    • spinal cord
    • CNS such as Duchenne muscular dystrophy, myasthenia, amyotrophic lateral sclerosis, Guillain-Barrè syndrome, etc. (Berliner 2016)
  • Fever
  • hypoxia
  • Metabolic acidosis (Herold 2020)
  • Medication such as beta blockers, NSAIDs, acetylsalicylic acid, platelet aggregation inhibitor ticagrelor (Berliner 2016)

The respiratory sensation is a consequence of interactions between

• the efferent (outgoing motor) output of the brain to the respiratory muscles (so-called feed-forward) and
• the afferent (incoming sensory) output of receptors throughout the body (so-called feedback) and
• the integrative processing of this information.

In the medulla and the carotid body (glomus caroticum) chemoreceptors are activated by hypoxemia, acute hypercapnia and acidemia. This leads to stimulation of other receptors causing an increase in ventilation.

Bronchospasm stimulates mechanoreceptors in the lungs, leading to a feeling of chest tightness. Also contributing to the feeling of tightness are the J- receptors and pulmo- vascular receptors activated by acute changes in pulmonary artery pressure.

The intensity of the breathlessness is further increased by a discrepancy between the feed-forward message to the ventilatory muscles and the feedback from the receptors, as is the case in asthma or COPD.

Acute anxiety in dyspnea increases severity by altering the interpretation of sensory data or by causing anxiety to produce breathing patterns that exacerbate physiological abnormalities (Kasper 2015).

In most respiratory system diseases, alterations in the mechanical properties of the lungs and/or chest wall are present. Some respiratory system disorders also stimulate pulmonary receptors.

Disorders of the cardiovascular system, on the other hand, lead to problems of gas exchange with stimulation of pulmonary and / or vascular receptors (Kasper 2015).

In patients with polio, induced spinal anesthesia or induced respiratory muscle paralysis, dyspnea does not occur immediately. Therefore, it can be assumed that the activation of the respiratory muscles is not essential for dyspnea. Only the reflex chemostimulation by the increasing CO2 causes dyspnea (Hayen 2013).

Depending on the pathophysiological mechanisms, the symptom of dyspnea arises in a variety of ways and is therefore described differently.

• Impaired left ventricular function:

It results from increased pressure in the pulmonary capillaries and leads to typical exertional dyspnea. Orthopnea and paroxysmal nocturnal dyspnea are also typical but not pathognomonic.

The following underlying mechanisms are discussed:

- progressive deconditioning

- weakness of the respiratory muscles

- early onset lactic acidosis due to reduced cardiac output

Patients with heart failure describe their problems as feeling difficult to breathe, hungry for air, suffocating (Weingärtner 2004).

• Obstructive pulmonary disease:

In these patients there is an increased ventilatory demand with a simultaneous reduced ventilatory capacity, a so-called ventilation-perfusion mismatch.

In emphysematics there is also an increased dead space ventilation and a reduced ventilatory recoil with reduced oxygen uptake.

In acute exacerbation, progressive hypercapnia results in a symptom of breathlessness.

Patients with COPD, for example, describe their dyspnea as a hunger for air and heavy breathing (Weingärtner 2004).

They are more likely to experience slowed but deep breathing (Kroegel 2014).

• Restrictive / parenchymal lung disease:

Already during the examination, a pronounced tachypnea is noticeable, which presents itself laboratory-chemically as lowered pCO2 values.

The stiffened lung tissue leads to reduced lung volumes, the compliance of the lung is reduced and due to the change in the longitudinal tension adaptation in the area of the respiratory muscles there is an increase in respiratory distress with reduced O2 values.

These patients describe their breathing as shallow, straining and wheezing (Weingärtner 2004). They are found to have an increase in ventilation or respiratory rate (Kroegel 2014).

• Pulmo- vascular diseases:

The mechanisms present in e.g. pulmonary embolism that lead to dyspnoea are controversial so far. The activation of vascular receptors, stimulation of the J-receptors, mechanical alteration of the lung tissue, reduction of the cardiac output and decrease of the O2-saturation are discussed.

In pulmonary hypertension, activation of vascular receptors in the pulmonary circulation leads to dyspnea.

Patients describe their breathing as comparatively rapid (Weingärtner 2004).

• Neurogenic / neuromuscular lung diseases:

In this case, the increasing weakness or paralysis of the respiratory muscles leads to dyspnoea, which can develop into complete respiratory failure.

The patients describe their breathing as strained and shallow (Weingärtner 2004).

• Already in the emergency room, it must be immediately clarified whether there is a vital threat to the patient. Indications for this are:
  • rapid development of dyspnea
  • Respiratory rate > 20 / min
  • Oxygen saturation SpO2 < 90 % (Herold 2020).

The need for hospitalization should be based on the criteria of the German Appropriateness Evaluation Protocol (G-AEP) (Hauswaldt 2017).

The G-AEP includes 6 categories:

- Category A: Severity of illness

- Category B: Intensity of treatment

- Category C: Surgery and invasive measures

- Category D: Comorbidities

- Category E: Need for intensive care

- Category F: Social factors (Weid 2011)

Medical history should be obtained:

• occupational history with possible indications of occupational lung diseases
• clarify risk factors for coronary heart disease
• Detailed history regarding the temporal occurrence of dyspnea:

Nocturnal dyspnea:

Nocturnal dyspnea is most likely to indicate heart failure or asthma (Kasper 2015).

Acute intermittent episodes of dyspnea:

They are most commonly found in patients with myocardial ischemia, bronchospasm, or pulmonary embolism (Kasper 2015).

Chronic persistent dyspnea:

Chronic persistent dyspnea occurs predominantly in interstitial lung disease or chronic thromboembolic disease (Kasper 2015).

Positional changes:

Complaining of dyspnea in the upright position that improves with supine positioning-so-called platypnea-may suggest left atrial myxoma or hepato-pulmonary syndrome (Kasper 2015).

Physical examination:

The physical examination should specifically include:

• Signs of increased work of breathing present such as supraclavicular retractions, use of accessory respiratory muscles, tripod posture, etc.?
• Measurement of respiratory rate
• Pulsus paradoxus?
• Speaking in complete sentences not possible because of shortness of breath?

If the patient cannot speak in complete sentences without taking another deep breath, this indicates respiratory impairment with reduced vital capacity or stimulation of the regulator.

• Signs of anemia present such as pale conjunctivae?
• Signs of cirrhosis present such as gynecomastia, spider naevi?
• Chest symmetrical?
• Percussion of the thorax (Kasper 2015).
• Auscultation of the thorax:
  • Inspiratory stridor with laryngospasm. Tracheal stenosis, glottic edema.
  • expiratory stridor in bronchial asthma, COPD (Herold 2020).
  • absent breath sound unilaterally
    • plus hypersonoric tapping sound in pneumothorax
    • plus attenuation in large pleural effusion or atelectasis (Herold 2020)
  • absent vocal fremitus in diaphragmatic elevation and pleural effusion
  • moist rales
    • plus sounding RGs (plus fever) in pneumonia
    • plus non-sounding RGs in pulmonary edema and left heart failure (Herold 2020)
  • Hyperventilation associated with paresthesias?
  • Auscultatory unremarkable lung findings in fluid lung = interstitial pulmonary edema (only visible on standing chest x-ray) or pulmonary embolism possible (Herold 2020)
• Chest pain in pulmonary embolism, ACS, pneumothorax (Herold 2020).
• cardiological examination:
  • Indications of increased jugular venous pressure
  • Edema
  • Auscultation of heart sounds
• abdominal examination:
  • Inward movement on inspiration indicates diaphragmatic weakness
  • Rounding of the abdomen on exhalation indicates pulmonary edema
• Joint swelling or deformity may indicate a collagen vascular process (Kasper 2015)

Chest X-ray

A chest x-ray should always be obtained in the presence of dyspnea.

• Hyperinflation:

Hyperinflation indicates obstructive lung disease.

• Low lung volume:

Low lung volume may indicate fibrosis, interstitial edema, dysfunction of the diaphragm, or limited chest wall motion.

• Lung Parenchyma:

Lung parenchyma may provide evidence of emphysema or interstitial disease such as pulmonary edema = fluid lung.

• Vascular System:

In the upper regions of the lungs, a prominent pulmonary vasculature indicates pulmonary venous hypertension.

Centrally enlarged pulmonary arteries may indicate pulmonary arterial hypertension.

• Heart:

An enlarged cardiac silhouette indicates dilated cardiomyopathy or valvular disease.

• Pleura:

Bilateral pleural effusions are typical of heart failure and some collagenous vascular diseases.

Unilateral effusions can occur with pulmonary embolism, carcinoma, or heart failure.

(Kasper 2015)

Thoracic CT

A chest CT is recommended in the presence of pulmonary embolism or for further evaluation of the lung parenchyma in interstitial disease, for example (Kasper 2015). It can also be used to identify the percentage of emphysematous lung (Berliner 2016).

12- channel ECG

This may reveal evidence of ventricular hypertrophy, a previous or acute myocardial infarction (Kasper 2015 / Berliner 2016), arrhythmias, signs of right heart strain (Steffen 2008).

Transthoracic echocardiography

Echocardiography is indicated when there is evidence of relevant right heart strain (Berliner 2016), such as pulmonary hypertension, systolic dysfunction, or valvular disease (Kasper 2015).

Spirometry

A lung function should be performed for further diagnosis in all patients with dyspnea (Weingärtner 2004). Functional dyspnea is usually accompanied by hypocapnia with respiratory alkalosis with decreased pCo2 and bicarbonate plus increased pH.

However, hypocapnia can also be present in organically induced dyspnea, so further diagnostic clarification is required in this case (Steffen 2008).

Caution: In hypercapnia, a drop in pH < 7.25 indicates respiratory decompensation (Kroegel 2014).

Bronchoprovocation test

A bronchoprovocation test should be performed especially in patients with a history of bronchial asthma (Kasper 2015).

Broncholysis test

This can be used to distinguish reversible respiratory obstructions from irreversible ones (Steffen 2008).

Cardiopulmonary exercise test

In patients who have evidence of both pulmonary and cardiac disease, a cardio-pulmonary exercise test should be performed to determine which organ is responsible for the dyspnea.

If maximal ventilation is achieved during maximal exercise and hypoxemia, bronchospasm, or an increase in dead space occur, the respiratory system is most likely the cause of the problem.

However, if heart rate is > 85% of maximum, blood pressure rises excessively or drops during exercise, anaerobic threshold is reached early, O2- pulse drops (O2 / heart rate ratio is an indicator of stroke volume), or ECG shows evidence of ischemia, a disease of the cardiovascular system is most likely the cause of dyspnea (Kasper 2015).

Calculation of the Wells- Score

The Wells- Score is used to estimate the risk of pulmonary embolism:

• 1.5 points in case of pulmonary embolism or deep vein thrombosis
• 1.5 points for heart rate > 100
• 1.5 points for surgery or immobilization in the last 4 weeks
• 1 point for haemoptysis
• 1 point for active cancer
• 3 points for clinical signs of deep vein thrombosis
• 3 points for alternative diagnosis less likely than pulmonary embolism

The likelihood of pulmonary embolism is . with 3-step grading:

- low at 0 - 1 points

- intermediate with 2 - 6 points

- high with ≥ 7 points

Probability of pulmonary embolism on 2-tiered classification:

- unlikely at 0 - 4 points

- probable at ≥ 5 points (Berliner 2016)

• Determination of laboratory chemical parameters for inflammation, ischemia and metabolic diseases (Steffen 2008)

also:

• brain natriuretic peptide = BNP (Brain natriuretic peptide).

This should be determined to assess heart failure or in case of right ventricular strain e.g. pulmonary embolism (Berliner 2016). In both cases it is elevated (Kasper 2015).

• D- dimers

D- dimers have a high negative predictive value, but an elevation is non-specific and therefore not suitable as a screening test of pulmonary embolism (Berliner 2016).

• Troponins

If there is clinical evidence of acute coronary syndrome, troponin I and troponin II should be determined. Cardiac troponins may also be elevated in acute pulmonary artery embolism with relevant right heart involvement (Berliner 2016).

• Fibrinogen
• Creatinine
• CRP (Berliner 2016)
• Blood gas analysis

Decreased pCO2- due to tachypnea is found in patients with restrictive / parenchymal lung disease (Weingärtner 2004) and hyperventilation.

The first thing to check for is evidence that the patient is in vital danger:

• rapid development of dyspnea
• respiratory rate > 20 / min
• oxygen saturation SpO2 < 90 % (Herold 2020)

If the patient is in vital danger, the vital parameters such as pulse, blood pressure, oxygen saturation are to be determined immediately and, depending on this, further procedures such as intensive care monitoring, invasive ventilation, etc. are to be initiated (Berliner 2016).

In all other cases, the focus is on diagnostics.

The necessity of an inpatient stay should be based on the criteria of the German Appropriateness Evaluation Protocol (G-AEP) (Hauswaldt 2017).

For more details, see "Diagnostics" above.

Oxygen:

For patients with advanced heart or lung disease, oxygen therapy may be useful, especially if the patient is already hypoxic at rest.

For patients with COPD, long-term oxygen therapy (LTOT) is recommended for stable COPD above a resting PaO2 ≤ 7.3 kPa.

Supplemental oxygen reduces mortality in chronically hypoxic patients. However, there are conflicting data regarding the alleviation of respiratory distress (Coccia 2016).

Pulmonary rehabilitation:

Pulmonary rehabilitation is an essential part of treatment for all patients with chronic lung disease.

The goals of rehab are:

• Reduction of exertional dyspnea
• Improved exercise tolerance
• Reduction of self-reported dyspnea on exertion.

The main component is physical exercise, in addition to improving conditioning, desensitization to dyspnea, pacing of activities, training to improve inhalation technique, breathing technique, and medication adherence (Coccia 2016).

In studies, air hunger has been shown to elicit a stronger affective response than increased effort or increased work of breathing. Pulmonary rehabilitation can reduce respiratory distress by altering this dimension (Kasper 2015).

Noninvasive ventilation:

Non-invasive ventilation may alleviate dyspnea by relieving the respiratory muscles, but there are few studies with dyspnea as an endpoint (Coccia 2016).

Cold air:

Patients often report that there is relief from dyspnea with exercise in cool air (Coccia 2016).

Opioids:

The most studied drugs for dyspnea are opioids. In the short term, they relieve dyspnea in interstitial disease, advanced COPD, carcinoma and CCF (carotid cavernous fistula).

Studies regarding long-term efficacy are conflicting and limited (Coccia 2016).

Increased respiratory rate on admission for dyspnea with vital threat is a predictor of poor prognosis with frequent intensive care stays and higher mortality (Berliner 2016).

Medically unexplained dyspnea is associated with increased susceptibility to acute hypercapnia (Kasper 2015).

1. Berliner D et al. (2016) Differential diagnosis of shortness of breath. Dtsch Arztebl Int (113) 834 - 845.
2. Coccia C B I et al (2016) Dyspnoea: pathophysiology and a clinical approach.S Afr Med 106 (1) 3236 DOI: 10.7196/SAMJ.2016.v106il.10324
3. Gerok W et al (2007) Internal medicine: reference work for the specialist. Schattauer Verlag Stuttgart / New York 1508
4. Hauswaldt J, Blaschke S (2017) Dyspnoea Der Internist (58) 925 - 936.
5. Hayen A et al (2013) Understanding dyspnea as a complex individual experience. Maturitas (76) 45 - 50
6. Herigstad M et al (2011) Dyspnea and the brain. Respir. Med. 105 (6) 809 - 817
7. Herold G et al (2020) Internal medicine. Herold Publishers 328 - 329
8. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 47e - 1 - 47e - 5
9. Kroegel C et al (2014) Clinical pulmonology: the reference work for clinic and practice. Georg Thieme Verlag Stuttgart / New York
10. Steffen M H et al. (2008) Internal medicine differential diagnosis: selected evidence-based decision processes and diagnostic pathways. Schattauer Verlag Stuttgart / New York 179 - 183
11. Weid S et al. (2011) Possibilities of performance-based remuneration of non-employed physicians in the inpatient sector: an activity-based costing using the example of varicose vein patients. Universitätsverlag der Technischen Universität Berlin 26
12. Weingärtner O et al (2004) Pathophysiology and differential diagnosis of dyspnea. Heart (29) 595 - 601