on 25-Oct-2020 (Sun)

In contrast, increased voluntary motor drive to respiratory muscles, which originates in the cerebral cortex (95, 96), predominantly evokes a perception of respiratory effort (58, 61), which, in healthy volunteers, is not as unpleasant as air hunger (97).

Mechanoreceptors in the lungs, airways, and chest wall provide afferent information about achieved pulmonary ventilation and can inhibit (relieve) air hunger/unsatisfied inspiration (98–103)

Unsatisfied inspiration or air hunger is not specific to any particular disease or stimulus

A consistent finding across experimental exercise and clinical studies is that patients with a variety of conditions (or normal subjects with chest wall corseting) report greater difficulty and discomfort during inspiration compared with expiration (inspiratory difficulty)

This suggests that, in susceptible individuals, air hunger may occur even in the absence of reduced ventilatory capacity. Factors such as excessive ventilatory drive or impaired perception of achieved ventilation may play a role. There also may be a role for increased sensitivity to CO₂ (which may, in turn, have a component of genetic predisposition) or excessive response to cerebral alkalosis or hypoxia due to hyperventilation-induced hypocapnia (118, 124)

A core pattern has emerged: dyspnea activates cortico-limbic structures (134–143) that also subserve interoceptive awareness of homeostatic threats such as thirst and hunger (144–148) or pain (134, 137–140, 149–152)

There is good evidence that opioid drugs reduce dyspnea (see E valuation and T reatment ). Laboratory studies in healthy subjects show that opioids reduce the discomfort of air hunger (166) but not the discomfort of work or effort (167).

Opioids likely act both by depressing spontaneous respiratory drive (thus reducing corollary discharge), and by modulating cortical activity, as they do in pain

In addition to laboratory, radiographic, and clinical studies, the words or phrases patients use to describe the quality of the breathing discomfort ( Table 3 ) may provide insight into the underlying pathophysiological mechanisms (27, 29–32, 36).

Chest tightness may be relatively specific for dyspnea due to bronchoconstriction ( 30, 67, 68, 74, 132). Sensations of “air hunger” and “inability to get a deep breath,” which probably represent the combined effects of increased drive to breathe and limited tidal volume, are commonly seen in association with dynamic hyperinflation (31, 86) and other conditions characterized by restrictive mechanics (e.g., heart failure or pulmonary fibrosis). Sensations of effort, suffocation, and rapid breathing have been found to characterize CO₂-induced panic attacks in patients diagnosed with panic disorder (119), but are nonspecific (200)

Although supplemental oxygen improves mortality in chronically hypoxemic patients with COPD, there are conflicting data about its ability to relieve breathlessness (220–224)

Oxygen therapy may be useful for patients with advanced heart or lung disease, in particular those who are hypoxemic at rest or with minimal activity (204, 212, 213, 224, 230)

The receptors are placed throughout the bronchial tree and, although in a lesser extent, also in other areas: ear, paranasal sinuses, pleura, diaphragm, pericardium and esophagus

Schematically, we may distinguish four different phases of cough, as a vital reflex arc, the first of which is a part in the afferent pathway while the last three in the efferent one (2)

Since the result of the cough reflex arc is the production of an airflow, the determinant factor of cough efficacy is the operational volume of the lung (3), which in turn relies on the strength and coordination of respiratory and laryngeal muscles as well as on lung mechanics

The decrease of operational volume of the lung can be the consequence not only of a weakness of respiratory muscles, but also of the expiratory flow limitation and lung hyperinflation

CPF evaluation is clinically relevant and it can be considered an overall parameter of cough efficacy (7)

The measurement of cough efficacy should be a routine assessment in patients suffering from progressive neurological disorders with lung involvement and in patients who are at high risk of an ineffective cough

Moreover, in case of a documented impairment of respiratory muscle function, an arterial blood-gas analysis may be requested to ascertain whether a hypoxemic-hypercapnic respiratory failure due to a ventilatory pump impairment may occur

Moreover, in patients with COPD the use of bronchodilators, such as beta2-agonists or muscarinic antagonists, can significantly reduce the exacerbation rate and this effect might be linked to an improvement in operational volume of the lung and, accordingly, to a more effective cough

Under normal conditions cough serves an important protective role in the airways and lungs, but in some conditions it may become excessive and nonproductive, and is troublesome and potentially harmful to the airway mucosa

In addition, more airway receptors are in the external auditory canals, eardrums, paranasal sinuses, pharynx, diaphragm, pleura, pericardium, and stomach. These are probably mechanical receptors only, which can be stimulated by triggers such as touch or displacement

These attributes can be used to identify at least three broad classes of airway afferent nerves:

1. Rapidly Adapting Receptors (RAR)

2. Slowly Adapting Stretch Receptors (SARs)

3. C-Fibers

RARs are activated by stimuli that evoke bronchospasm or obstruction resulting from mucus secretion or edema. Substances such as histamine, capsaicin, substance P, and bradykinin activate RARs in a way that can be markedly inhibited or abolished by preventing the local end-organ effects that these stimuli produce (e.g. bronchospasm and mucus secretion)

RAR activation initiates reflex bronchospasm and mucus secretion through parasympathetic pathways

RARs may act synergistically with other afferent nerve subtypes to induce coughing

SARs are highly sensitive to the mechanical forces that are put on the lung during breathing. SAR activity increases during inspiration and peaks just prior to the initiation of expiration [13]

SARs are thus thought to be the afferent fibers involved in the Hering-Breuer reflex, which terminates inspiration and initiates expiration when the lungs are adequately inflated

SAR activation results in the central inhibition of respiration and the inhibition of the cholinergic drive to the airways, leading to decreased phrenic nerve activity and decreased airway smooth muscle tone (due to a withdrawal of cholinergic nerve activity) [ 14]

SARs may facilitate coughing by a central cough network via activation of brainstem second-order neurons of the SAR reflex pathway.

The majority of afferent nerves innervating the airways and lungs are unmyelinated C-fibers

In addition to their conduction velocity (< 2 m/s), airway vagal afferent C-fibers are distinguished from RARs and SARs by their relative insensitivity to mechanical stimulation and lung inflation. C-fibers are further distinguished from RARs by the observation that they are directly activated by bradykinin and capsaicin, not indirectly through effects on smooth muscle or the airway vasculature

Reflex responses evoked by C-fiber activation include increased airway parasympathetic nerve activity, and the chemoreflex, characterized by apnea (followed by rapid shallow breathing), bradycardia, and hypotension

Sex-related differences in cough reflex sensitivity explain the observation that women are more likely than men to develop chronic cough [18-20]

The specific pattern of the cough depends on the site and type of stimulation. Mechanical laryngeal stimulation results in immediate expiratory stimulation (sometimes termed the expiratory reflex), probably to protect the airway from aspiration; stimulation distal to the larynx causes a more prominent inspiratory phase, presumably to generate the airflow necessary to remove the stimulus.

Cough-induced rib fractures are another painful and potentially serious complication of chronic cough. Fractures often involve multiple ribs, particularly ribs five through seven. Women with decreased bone density are at the greatest risk of this complication; however, fractures can occur in patients with normal bone density as well [24]

During vigorous coughing, intrathoracic pressures may reach 300 mm Hg and expiratory velocities approach 800 kilometers per hour [22]

A nonproductive cough is a well-recognized complication of treatment with angiotensin converting enzyme (ACE) inhibitors, occurring in up to 15% of patients treated with these agents [25]. Although the pathogenesis of the cough is not known with certainty, it has commonly been hypothesized that accumulation of bradykinin, which is normally degraded in part by ACE, may stimulate afferent C-fibers in the airway [26]

Another rare cause of chronic cough is Holmes-Adie syndrome due to autonomic dysfunction affecting the vagus nerve [36] patients present anisocoria, abnormal deep tendon reflexes, and patchy areas of hyperhidrosis or anhidrosis

Irritation of the external auditory canal by impacted foreign bodies or cerumen is another unusual cause of chronic dry cough [33]. The etiology of the ‘ear-cough’ (or oto-respiratory) reflex is related to stimulation of the auricular branch of the vagus nerve (Arnold's nerve) [34,35]

Differences among several sites from which cough stimuli can originate may result in variations in the sounds and patterns of coughing

Laryngeal stimulation produces a choking type of cough without a preceding inspiration

Inadequate mucociliary clearance mechanisms (as in bronchiectasis or cystic fibrosis) may produce a pattern of coughing with less violent acceleration of air and a sequence of interrupted expirations without any intervening inspiration

Since cough is an important defensive reflex, required to maintain the health of the lungs, people who do not cough effectively are at risk of atelectasis, recurrent pneumonia, and chronic airways disease from aspiration and retention of secretions

The vagus is the most important afferent nerve, although the glossopharyngeal and trigeminal nerves may operate, depending on the receptors involved

The combination of a high airflow and airway narrowing results in the expulsion of an airstream with a linear velocity sometimes nearing the speed of sound.

With large lung volumes, only the trachea and large bronchi are compressed; with smaller lung volumes, more distal airways are also narrowed

Variation in sounds of coughing is due to several factors, including the nature and quantity of secretions, anatomic differences and pathologic change of the larynx and other air passages, and the force of the cough

With an adequate function of the mucociliary escalator, the cough has no additional benefit in removing the amount of secretions formed under normal conditions. In pathologic states, however, when the mucociliary function is ineffective or insufficient because of the quantity or alteration of the physical properties of secretions, the cough becomes essential for airway clearance

Mucous sputum is clear or translucent and viscous, containing only small numbers of microscopic elements. Purulent sputum is off-white, yellow or green, and opaque. It indicates the presence of large numbers of white blood cells, especially neutrophilic granulocytes. In asthmatics, the sputum may look purulent from the eosinophilic cells. Red coloration, uniform or streaky, is usually due to its mixture with blood. Carbon particles discolor the sputum gray (as in cigarette smokers) or black (as in coal miners or with smoke inhalation)

Pathologic conditions causing the cough are usually the ones that irritate the airways, increase their irritability, result in their deformation, or increase the tracheobronchial secretions

Sputum production with coughing occurs when the respiratory tract secretions are beyond the ability of the mucociliary mechanism to deal with them

Inflammation of the respiratory tract mucosa, from infectious or noninfectious causes, results in hyper-reactivity of the cough receptors. This results from the alteration of the surface epithelium, making them more sensitive to the cough-producing effect of commonly occurring mild irritants such as cold air, respiratory pollutants, deep or fast respiration, and excessive use of the larynx. At times, the mechanical irritation of coughing itself brings about more coughing

As chronic bronchitis and lung cancer are very uncommon among nonsmokers, a chronic persistent cough has a different significance in this population. Airway hyperreactivity, the hallmark of bronchial asthma, is a rather common condition in which the cough may be the predominant or even the sole manifestation

Left-sided heart failure not only results in a cough with acute pulmonary edema but also may be a cause of a chronic nocturnal cough. Recurrent aspiration is another condition in which the cough characteristically occurs in a supine position. Foreign-body aspiration should always be considered in the differential diagnosis of the chronic cough. After the initial coughing or choking episode at the time of its aspiration, the cough may restart and continue long after the incident

Chronic expectoration of large amounts of purulent and foul-smelling sputum is strongly suggestive of bronchiectasis. Sudden production of such a sputum in a febrile patient indicates a lung abscess. Rust-colored purulent sputum in pneumococcal pneumonia, currant jelly and sticky sputum in klebsiella pneumonia, and blood-tinged foamy sputum in pulmonary edema are other examples in which the diagnosis of the underlying disease is strongly suggested

Myth seeks to answer perplexing questions but does so in such a way as to create and preserve a kind of civic coherence. The mythology of a people is the basis on which they recognize themselves as a people and have a coherent relationship, not only to each other but with their own past. To some extent, philosophy is disruptive in this regard. The enterprise is not an essentially civic one. It does not begin with a settled position on political and moral matters, then seek ways to enshrine the settled view. Rather, the mission is a broadly epistemological one. The search, as we shall discover, is the search for truth.

The questions that mythology must set out to answer are not unlike the questions that philosophy sets out to answer. We can identify three overarching issues that consume much of the subject matter of philosophy: the problem of knowledge, the problem of conduct, and the problem of governance.