https://meditropics.com/559-2/
Desh Deepak, Tome Kamgo, Jyoti Sharma, Department Of Respiratory Medicine, ABVIMS & Dr. RML Hospital, New Delhi
Introduction
Chronic respiratory failure is a condition that results in the inability to effectively exchange carbon dioxide and oxygen and induces chronically low oxygen levels with or without high carbon dioxide levels. The conditions that may lead to chronic respiratory failure are diseases of the lung; obstructive, restrictive or vascular, chest wall & neuromuscular diseases, decreased central drive and OHS.
Chronic respiratory failure is a challenging condition to manage, as there are difficulties not only in the treatment but also even in the assessment of these patients. Necessities like attending a medical facility often requires concerted efforts of the family members. Waiting in OPD or emergency areas can be health hazard for these patients besides being an arduous task. In this chapter, we shall discuss COPD as a prototype to elucidate various challenges in the management of chronic respiratory failure and then discuss certain specific problems faced in some other common conditions leading to chronic respiratory failure.
COPD
Chronic obstructive pulmonary disease (COPD) is the most common cause of respiratory failure. Ideally, it should be detected and treated in the early stages before respiratory failure occurs. Most patients do not follow appropriate treatments for their disease because often they underestimate it and sometimes even consider it self-inflicted. These patients must be dealt in an empathetic manner rather than a retributive attitude.
Prognostic factors associated with poor survival in COPD include low FEV1 (10% mortality per year for FEV1 less than 35%), active smoking status, hypoxemia, low exercise capacity, severe dyspnea, inability to walk 100m without stopping (because of breathlessness), anaemia, frequent exacerbations, comorbid illnesses and low diffusion capacity. Assessment of such varied factors needs significant time, understanding and involvement of the treating physicians. These patients are often unable to perform even simple spirometry. Measurement of diffusion capacity with single breath needs patients to hold the breath steady for 10 seconds, which is often difficult. Availability of multiple breath method may be limited at centres. Patients who have FVC less than 1.2-1.3 litres cannot be assessed for diffusion capacity by most of the standard machines. Simple proven tools such as BODE index help the physicians make a reliable assessment. These patients may not be able to perform a six minute test either because of comorbidities or dyspnoea. Using ADO (age, dyspnea scale, obstruction level) index is an option in these patients. Pulse oximetry should be used as far as possible but cannot always substitute for the arterial blood analyses. Using arterialised capillary blood is an option used in such a situation. Assessment of co-morbities requires these patients to visit various specialities and their investigative departments. Provision of these services by an internist or under one umbrella where synchronised services can be provided at one place goes a long way in making management of these patients easier.
each stage. It is rare for a smoker to progress successfully through these stages in the initial quit attempt. The cycle will likely be repeated several times before a prolonged abstinence, which is remission, is achieved. Thus, the clinician must be encouraging and willing to support repeated attempts. The National Cancer Institute’s (NCI) recommended model for smoking intervention is based on “the five A’s,” emphasizes the role of medical professionals to ask patients about their smoking status, assess their willingness to make a quit attempt, advise smokers to stop, assist them in their stop smoking efforts, and arrange for follow-up visits to support the patient’s efforts. This approach utilizes brief intervention techniques and emphasizes the role of physicians as facilitators in the quitting process. Group Counseling includes lectures, group interactions, exercises on self-recognition of one’s habit, some form of tapering method leading to a quit day, development of coping skills, and suggestions for relapse prevention. One-year success rates associated with group counseling programs are typically in the 15% to 35% range. Telephone counseling is an effective alternative.
Pharmacologic treatment
First-line pharmacological drugs for smoking cessation are NRTs, varenicline and bupropion SR. These drugs have scientific, well-documented efficacy when used for 2–3 months. These medications, in combination with counselling, have also shown to be effective for smokers with COPD, who often seem more reluctant to quit smoking.
Nicotine Replacement Therapies
NRTs (patches, gum, inhaler, nasal spray, lozenge/tablets and oral spray). NRT is usually started on the scheduled quit day. The trans-dermal systems provide the slowest delivery of nicotine but maintain steady-state levels throughout the day. The other formulations allow episodic dosing. A common practice is to combine a trans-dermal system with another formulation, a “patch-plus” regimen. This allows a smoker to increase nicotine delivery at times of urges. Clinical trial data supports better success with combined NRT compared to monotherapy.
Bupropion
Bupropion is an antidepressant, and it is also effective as an aid for smoking cessation. It is believed to act by potentiating dopaminergic and noradrenergic signaling. Combination of nicotine replacement with bupropion has been assessed and appears more effective than either agent alone. The currently recommended dose is 150-mg daily for 3 days followed by 150-mg twice daily. Because the drug is excreted slowly, steady state-levels are achieved after 6 to 7 days. For this reason, the quit date should be scheduled after a week of therapy so that blood levels are established. 12-week course is commonly recommended. With prolonged therapy, there is an increase in secondary quits and therapy for 1 year resulted in more quits than therapy for 7 weeks. Most common adverse effects are dry mouth, insomnia, agitation, and headache. In combination with nicotine replacement, an increase in blood pressure may also occur. Bupropion is contraindicated among those predisposed to seizures, or with anorexia nervosa or bulimia. Bupropion and varenicline labels contain a black box warning, suggesting that patients and their caregivers should be alerted to the possibility of neuropsychiatric symptoms and patients should be monitored for changes in behaviour, hostility, agitation, depressed mood, suicidal ideation and suicide attempts.
Varenicline
Varenicline is a partial agonist at the (alpha4)(beta2) nicotinic receptor. As such, it can partially activate the receptor thereby mitigating withdrawal symptoms. In addition, by occupying the receptor, it can prevent nicotine from acting, and thus can reduce the rewarding and reinforcement effects associated with nicotine. This may be particularly important in preventing a lapse from becoming a full relapse once abstinence has been achieved. Varenicline is given orally. Usually medicine is started at 0.5-mg once daily for 3 days followed by 0.5-mg twice daily for 4 days and then 1-mg twice daily for 3 months. Individuals who have achieved abstinence at 3 months may have less relapse if therapy is continued for an additional 3 months. A quit date is usually recommended for 1 week after starting medication. The most common adverse reactions are nausea, insomnia, visual disturbances, syncope, and skin reactions. The most serious concerns with varenicline have been with psychiatric and cardiovascular side effects. Varenicline has also been associated with accidental injuries from falls and vehicular accidents. This has resulted in an FDA advisory regarding operating heavy machinery while using varenicline.
Pharmacotherapy for COPD
Inhaled bronchodilators in COPD are central to symptom management and given on regular basis to prevent or reduce symptoms. Regular or as needed use of SABA or SAMA improves FEV1 and symptoms. LABAs and LAMAs significantly improve the lung function, dyspnea, health status and reduce the exacerbation rates. Combination of LABA and LAMA increases FEV1 and reduces the symptoms as compared to monotherapy. Tiotropium improves the effectiveness of pulmonary rehabilitation in increasing the exercise performance.
An ICS combined with LABA is more effective than the individual components in improving lung function and health status in patients with exacerbation and moderate to very severe COPD. PDE4 Inhibitors like Roflumilast improve the lung function and reduce moderate to severe exacerbation in severe to very severe COPD with history of exacerbation. Mucolytics and anti-oxidant agents also reduce the risk of exacerbations in selected group of patients with COPD.
However, with the use of LABA or SABA, stimulation of beta2-adrenergic receptors can produce resting sinus tachycardia and has the potential to precipitate cardiac rhythm disturbances in susceptible patients. Exaggerated somatic tremor is troublesome in some older patients treated with higher doses of beta2-agonists, regardless of route of administration. With Inhaled anticholinergic drugs, the side effects are dryness of mouth, acute urinary retention in patients with bladder outlet obstruction and acute narrow angle glaucoma if sprayed in eye.
Inhaled Drug delivery:
Advantages of inhaled drug administration include rapid onset of action and the ability to deliver small drug doses directly to the lungs, minimizing systemic drug exposure. Device selection depends on drug–device availability, patient characteristics (e.g., age, cognitive function, manual dexterity) and patient preference. It is essential to demonstrate proper inhaler technique when prescribing a device. Inhaler technique should be assessed first before concluding that the current therapy requires modification.
There are three main types of devices used to deliver inhaled medication: pressurized metered-dose inhalers (pMDIs), dry powder inhalers (DPIs), and a soft mist inhaler (SMI).MDIs are small portable devices that protect the medication from contamination however, they are difficult to use correctly. Common drug administration errors include improper timing of actuation and inspiration and failure to inspire slowly and deeply. MDI accessory devices (e.g., spacers, valved holding chambers) decrease oropharyngeal drug deposition and reduce the need for precise “press and breathe” timing, but they are bulky, add to the cost of therapy, and must be regularly cleaned to reduce bacterial contamination and electrostatic charges within the chamber. The new Respimat device is a unique, multidose liquid inhaler that uses spring-loaded energy to generate a fine aerosol mist. DPIs are available as premetered devices that contain or accept single doses or as bulk reservoir devices. DPIs are breath actuated, requiring rapid and forcible inhalation to aerosolize and deliver the dose; most require inspiratory flow rates of 30 to 60 L/min. Elderly, and the patients with reduced lung function (e.g., during an acute exacerbation) may be unable to generate adequate inspiratory flow rates. Nebulizers aerosolize a solution or suspension by one of the three mechanisms: compressed air or oxygen (jet nebulizers), high-frequency ultrasonic energy (ultrasonic nebulizers), and vibrating mesh. Suspensions can only be aerosolized with jet nebulizers. Nebulizers are more expensive, require more dose.
The treatment modality that may reduce the progression of COPD is smoking cessation. In COPD, an intensive regimen of bronchodilators (e.g., β2-adrenergic agonists, anticholinergics, and theophylline) and anti-inflammatory therapy (e.g., corticosteroids) can correct respiratory failure by diminishing airway resistance, FRC, lung dead space volume, the alveolar– arterial O2 partial pressure gradient, and the work of breathing. However, the management of chronic respiratory failure in COPD goes far beyond pharmaco-therapeutics. The time, understanding, resources and motivation required to address each of the arms of chronic respiratory failure management makes it a daunting task. The following paragraphs discuss various aspects of management in these cases.
Smoking cessation
Non-pharmacologic approaches
Smoking cessation process involves five stages: pre-contemplation, contemplation, preparation, action, and maintenance. These stages are viewed as a continuum with smokers progressing sequentially through preparation and take more time to deliver a dose than other drug delivery devices. However, they require less patient cooperation and may b used by patients of all ages and abilities.
COPD and comorbidities
COPD often coexists with other diseases (comorbidities) that may have a significant impact on disease course. In general, the presence of comorbidities should not alter COPD treatment and comorbidities should be treated per usual standards regardless of the presence of COPD. Lung cancer is frequently seen in patients with COPD and is a main cause of death. Cardiovascular diseases are common and important comorbidities in COPD. Adverse effects and interactions of drugs with opposite mechanisms of actions is a challenge in these patients. Minimum required doses should be administered and titrated as per the clinical condition. Use of levo-salbutamol in place of salbutamol or LAMA in lieu of SAMA may be beneficial. Osteoporosis and depression/anxiety are frequent and important comorbidities in COPD which are often under-diagnosed, and are associated with poor health status and prognosis. Gastroesophageal reflux (GERD) is associated with an increased risk of exacerbations and poorer health status. When COPD is part of a multimorbidity care plan, attention should be directed to ensure simplicity of treatment and to minimize polypharmacy.
Exercise and rehabilitation
Pulmonary rehabilitation is defined as “a comprehensive intervention based on thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, education, self-management intervention aiming at behavior change, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence to health-enhancing behaviors.” Pulmonary Rehabilitation improves dyspnea, health status and exercise tolerance in stable patients. It also reduces hospitalization among patients who have had a recent exacerbation (≤4 weeks from prior hospitalization). It also leads to reduction in symptoms of anxiety and depression. Education is an integral component; even patients with severe disease can gain a better understanding of their disease and learn specific means to deal with problems. Instruction can be provided individually or in small groups, but it should be adapted to different learning abilities. Individual instruction and coaching may be provided on the use of respiratory therapy equipment and supplemental oxygen, breathing techniques, bronchial drainage, chest percussion, energy-saving techniques and self-care tips. The general philosophy is to encourage patients to assume responsibility for their own care and become partners with their physician in providing the care.
Breathing retraining techniques
Pulmonary rehabilitation typically includes instruction in breathing techniques, such as diaphragmatic and pursed lips breathing—techniques aimed at helping patients relieve and control breathlessness, improve their ventilatory pattern (i.e. slower respiratory rate and increased tidal volume), prevent dynamic airway compression, improve respiratory synchrony of the abdominal and thoracic musculature, and improve gas exchange.
EXERCISE
Exercise is important in pulmonary rehabilitation. Benefits are both physiological and psychological. Patients may increase their maximum capacity and endurance for physical activity, even though objective measures of lung function do not usually change. Patients may also benefit from learning to perform physical tasks more efficiently. Resistive training is also used commonly in rehabilitation and can lead to significant increases in muscle strength that are important for many activities of daily living. However it is costly and labor-intensive, considering the personnel, equipment, and expertise required. Simple exercises for upper limb and torso with readily available objects like water bottles as weights can be performed at home even by patients in advanced stages.
Oxygen therapy
Long-term oxygen therapy is indicated for stable patients who have:
- PaO2 at or below 7.3 kPa (55 mmHg) or SaO2 at or below 88%, with or without hypercapnia confirmed twice over a three-week period; or
- PaO2 between 7.3 kPa (55 mmHg) and 8.0 kPa (60 mmHg), or SaO2 of 88%, if there is evidence of pulmonary hypertension, peripheral edema suggesting congestive cardiac failure, or polycythemia (hematocrit> 55%).
Once placed on long-term oxygen therapy (LTOT) the patient should be re-evaluated after 60 to 90 days with repeat arterial blood gas (ABG) or oxygen saturation while inspiring the same level of oxygen or room air to determine if oxygen is therapeutic and still indicated, respectively.
LTOT has a significant beneficial effect on survival in patients with chronic hypoxemia. However, initiation of chronic home oxygen therapy can be a substantial burden for patients. Various studies have noted adherence to LTOT in only 45% to 70% of patients. The barriers to adherence are many and include patient concerns of addiction and dependency, embarrassment from the “stigma” that an oxygen delivery device represents with respect to a smoking-related disease, and the associated limitations on physical activity arising from bulky ambulatory oxygen sources. Therefore, appropriate counseling about the benefits and demands of oxygen therapy is necessary before beginning treatment. Consideration of oxygen source portability, social and home support available (e.g., from friends, family, or visiting nurses) and patient attitudes and beliefs when considering LTOT. Finally, the clinical needs to facilitate sufficiently close patient monitoring to ensure long-term benefit from therapy.
Techniques of oxygen administration
When choosing an oxygen delivery device for a given patient, consider the degree of hypoxemia, the specificity required with regard to setting the FIO2 (which depends on the patient’s respiratory control), and the patient’s minute ventilation. The oxygen flow that the device can deliver, the adjustability and precision of that delivery, and the comfort and cost of the device are additional considerations. Low-flow and variable performance oxygen devices such as nasal cannulae, simple oxygen masks or reservoir masks may be suitable for many patients.Low-flow systems deliver only a fraction of the patient’s minute ventilation as pure oxygen. The maximum flow in these systems is 15 L/min. Nasal cannula entrains a constant flow of pure oxygen, generally ranging from 2 to 6 L/min. At 6 L/min or higher, the patient may experience discomfort, excessive mucosal dryness, and epistaxis. Oxygen masks can deliver higher oxygen flow rates than nasal cannulae; they entrain less room air and, therefore, can generate a higher FIO2. In addition, the configuration of simple masks enables an enlarged reservoir of oxygen for inhalation. Flow rates for simple masks range from 5 to 12 L/min, which usually requires some room air to be entrained via the side ports of the mask to meet the patient’s minute ventilatory needs. Given the higher flow rates delivered using face masks, a humidifier is also often required. The flow rate of a simple mask should never be <5 L/min; below this level, carbon dioxide re-breathing may occur, along with an increased resistance to inspiration. Simple masks are also more uncomfortable, making eating and communicating challenging. A reservoir mask is similar to a simple mask but has an attached reservoir of 600 to 800 mL, resting below the patient’s chin. Generally, the mask provides flow between 8 and 15 L/min, which keeps the reservoir bag at least half full. Reservoir masks include partial re-breather and non re-breather types. When using a non rebreathing reservoir mask, oxygen flow should be set high enough to prevent deflation of the reservoir bag—usually about 15 L/min. Currently available masks do not fit securely enough to ensure a delivered FIO2 of 100%. Typically, these masks provide a maximum FIO2 of 80% to 90%; the FIO2 may be even lower (60%–80%) in the setting of very high minute ventilation. Some patients especially in advanced stages may need high flow fixed-performance oxygen devices such as air entrainment mask (venturi masks), high flow generators, high flow nasal cannula. The devices allow for a fixed FIO2 by providing very high flows of pure oxygen which exceed the patient’s minute ventilation, sometimes by a factor of four. Along with very high flow rates, the devices incorporate oxygen reservoirs whose volumes exceed the patient’s anatomical dead space. Since the FIO2 is predictable, high-flow devices are ideal for patients who have precise oxygen needs that should be neither exceeded nor unmet.
Nutritional support
In patients with very severe COPD (FEV1 less than 35% predicted) about half show protein–calorie malnutrition. Reasons for this include increased resting metabolic demands, inadequate caloric intake due to dyspnea and anorexia, and possibly elaboration of cachexia-associated inflammatory cytokines such as TNF-α, IL-1, and IL-6. For malnourished patients with COPD nutritional supplementation is recommended. This is based on findings of positive effects on body weight, fat mass and fat-free mass when nutritional supplementation is provided alone to COPD patients (especially if malnourished) and when used as an adjunct to exercise training. Those who do not respond to nutritional supplements can be tried on Ghrelin. It increases food intake and body weight, anti-inflammatory effects, and energy metabolism regulation.
Vaccination
Influenza vaccination is recommended for all patients with COPD. Pneumococcal vaccinations, PCV13 and PPSV23, are recommended for all patients > 65 years of age. The PPSV23 is also recommended for younger COPD patients with significant co-morbid conditions including chronic heart or lung disease.Covid19 vaccination should also be given to all COPD patients according to the guidelines of the govt of India. Tdap (dTap/dTpa) vaccination for adults with COPD who have not been vaccinated in adolescence for prevention of pertussis (whooping cough) is recommended internationally.
Interventional bronchoscopy and surgery
In selected patients with heterogeneous or homogenous emphysema and significant hyperinflation refractory to optimized medical care, surgical or bronchoscopic modes of lung volume reduction (e.g., endobronchial one-way valves, lung coils or thermal ablation) may be considered. Some of these therapies (vapor ablation and lung coils) are not widely available for clinical care in many countries. In selected patients with a large bulla, surgical bullectomy may be considered. In selected patients with very severe COPD and without relevant contraindications, lung transplantation maybe considered.
Ventilatory support
NIV is occasionally used in patients with stable very severe COPD. NIV may be considered of some use in a selected group of patients, particularly in those with pronounced daytime hypercapnia and recent hospitalization. However, in patients with both COPD and obstructive sleep apnea, there are clear indications for continuous positive airway pressure (CPAP).
End of life and palliative care
The goal of palliative care is to relieve the suffering of patients and their families by the comprehensive assessment and treatment of physical, psychosocial, and spiritual symptoms experienced by patients. Patients with a chronic life-limiting illness like COPD should be informed that, should they become critically ill, they or their family members may be in a position where they would need to decide whether a course of intensive care is likely to achieve their personal goals of care and they are willing to accept the burdens of such treatment.
Neuromuscular and chest wall diseases
Most neuromuscular diseases (NMD) are characterised by progressive muscular impairment leading to loss of ambulation, being wheelchair-bound, swallowing difficulties, respiratory muscle weakness and, eventually, death from respiratory failure. Rapidly progressive NMD are characterised by muscle impairment which worsens over months and results in death within a few years. Respiratory failure is the most common cause of morbidity and mortality in these patients with chronic or rapidly progressive NMD. Reduction in inspiratory muscle strength, with related ineffective alveolar ventilation and expiratory muscle weakness, and difficult airway secretions clearance, lead to chronic respiratory insufficiency, as well as to potentially life-threatening problems. Functional neuromuscular respiratory system can be divided into three main areas of function: (1) Ventilatory function determined predominantly by the inspiratory muscles; (2) Cough function, which is determined by inspiratory, expiratory, and glottic function; and (3) Swallowing and airway protection determined by glottic muscles. Each one of these three functional parts of the system may show evidence of impairment and contribute to neuromuscular respiratory failure, although dysfunction in each area is not always present at the same time.
Ventilatory assistance
Patients with chronic NMD, such as other myopathies, experience a slowly progressive reduction in respiratory muscle function. Therefore, they initially suffer from nocturnal hypoventilation and recurrent respiratory infections, progressing to daytime hypercapnia and eventually to death. Long-term mechanical ventilation (LTMV) delivered either invasively or noninvasively (NIV) is the main therapeutic intervention to support the respiratory muscle function and to increase life expectancy and health-related quality of life (QoL) in these patients.
Non invasive mechanical ventilation
Long-term NIV has improved survival in patients with some NMD, and improved the QoL in most patients. Usually, NIV is performed at night, but additional daylight hours of NIV are suggested as this may unload respiratory muscles and reverse breathlessness more effectively than night NIV alone. Compared to tracheostomy ventilation, NIV greatly simplifies administration of care, is more comfortable for patients and reduces costs. Night-time NIV means that patients are not restricted in the daytime and enables them to be cared for at home, whereas with long-term tracheostomy ventilation patients may need admission to healthcare services or highly trained and well-motivated home professional or familiar caregivers. Because of the advantages over tracheostomy ventilation in most patients and the consistency of supporting evidence, NIV should be considered as the preferred ventilatory modality for home mechanical ventilation in NMD patients. Although LTMV prolongs survival through both interfaces, NIV is preferred by patients over tracheostomy for speech, sleep, swallowing, comfort, appearance and security. Nocturnal NPPV treatment for NMD has been reported to improve symptoms of fatigue, daytime hyper-somnolenceand morning headaches as well as gas exchange. Availability of newer versions of Cuirass ventilators that provide negative pressure ventilation holds promise for these patients. These avoid the need for an interface that intereferes with talking or eating or a tracheostomy. However, these cannot be used in situations where there is a co-existing upper airway obstruction that needs to be splinted.
Glossopharyngeal breathing
Glossopharyngeal breathing (GPB) is the act of the glottis taking air and propelling it into the lungs. One breath usually consists of six to nine gulps of 60–100 mL each.GPB can permit lung volume recruitment by using the glottis rather than a manual resuscitator or volume cycling ventilator for air stacking. It can provide individuals with no inspiratory muscle function to have normal ventilation throughout daytime hours without using a ventilator and safety in the event of ventilator failure during sleep. The safety and versatility afforded by GPB are the keys to avoiding tracheostomy or removing one in favor of using noninvasive aids for neuromuscular ventilatory failure.
Clearing airways
Effective secretion clearance is critical for patients with chronic NMD to prevent atelectasis, pneumonia, acute respiratory failure and hospitalization. The use of airway clearance techniques, including assisted coughing techniques, both manual and mechanical, and secretion mobilization techniques, is strongly recommended. These techniques should always be included in the treatment of chronic NMD patients.
Cough can be assisted by manual and mechanical means.
Manually assisted coughing
Manually assisted coughing requires substantial lung inflation through air stacking or deep lung insufflation, followed by an abdominal thrust applied as the glottis opens. Manually assisted coughing requires a co-operative patient, good coordination between the patient and caregiver, adequate physical effort and often frequent application by the caregiver. Forced exhalation is augmented by pushing on the upper abdomen (i.e. abdominal thrust) or chest wall (i.e. anterior chest compression) in synchrony with the subject’s own cough effort.
Mechanical in-exsufflation
When manually assisted coughing is not enough, the most effective alternative is mechanically assisted coughing. The combination of mechanical in/ex sufflation with an abdominal thrust is a mechanically assisted cough. Mechanical in-exsufflation delivers deep insufflations followed immediately by deep exsufflations. Secretion mobilisation techniques that induce a more efficient airway secretion clearance are also helpful and include manual chest percussion and postural drainage. Provision of mechanical in-exsufflation in combination with standard chest physical treatments may improve the management of airway mucous obstruction in NMD.
End of life respiratory care
In patients with serious illness at the end of life, clinicians should regularly assess patients for pain, dyspnoea and depression, and administer therapies of proven effectiveness for pain, dyspnoea (including opioids and oxygen) and depression. Providing patients and their families with information about treatment options and anticipating possible future needs are crucial steps to appropriately tailor the management of the respiratory issues of NMD patients. NIV is often the only way to sustain NMD patients who decline endotracheal intubation and invasive mechanical ventilation. Since NMD are characterised by a progressive clinical deterioration, these patients must be involved in the decision-making process on treatment escalation, such as endotracheal intubation, tracheotomy and, eventually, the option of palliative care.
Interstitial lung disease
Chronic respiratory failure complicates the course of ILDs. This occurs usually with the progression of the disease and associated comorbid conditions. For management, identification of the underlying cause is crucial. This includes assessment of worsening of underlying ILD, onset of comorbidities or worsening of the existing comorbidities.
Causes of CRF in ILD include worsening of underlying ILD, COPD and emphysema, Small airway disease, Lung cancer, CHF, OSAS, Pulmonary embolism, Pulmonary hypertension etc.
Management and treatment includes identifying the specific type of ILD which is usually achieved by a multidisciplinary diagnosis. The assessment requires complete PFT with diffusion studies with its inherent problems as discussed above.
These patients some time need extensive blood work up in addition to a detailed clinical examination to rule out connective tissue disorders. Often the CT scans are ordered and done without proper ILD protocols that makes it difficult to interpret them. HRCT scans with 0.5 or 1 mm thickness scans, which may include prone and expiratory films are often required to identify specific ILDs. Details of occupational history and other environmental exposure need time and diligence to narrow down to the possible etiologies. Sometimes it may be difficult to reach a reasonable diagnosis in spite of all efforts, when a surgical biopsy of the lung is warranted. However, such patients are mostly high risk or unwilling for a major diagnostic surgical procedure. A reasonable best fit must be offered with focus on palliation in such cases.
Therapies for the underlying disease
Antifibrotic agents like Nintedanib and Perfinidone are used for IPF. Treatment with immunomodulating agents like corticosteroids, cyclophosphamide and mycophenolate are used regardless of the pattern of fibrosis for CTD ILDs. Methotrexate is the most common first line treatment for RA to prevent joint destruction. However due to potential of pulmonary toxicity with methotrexate use, it is seldom used for treatemt of RA ILD. These medicines have significant adverse effects and drug interactions. Also, it is difficult to assess response to these therapies as the clinical benefit may manifest in many months. Striking a balance between acceptable adverse effects and accrued benefit is often required.
Therapies for dyspnea
Resting hypoxaemia is a marker of advanced stage in chronic lung diseases. It is defined as resting PaO2 ≤ 55 mmHg or 56-59 mmHg with evidence of end organ damage (corpulmonale, polycythaemia and/or pulmonary hypertension).
Oxygen therapy improves exercise tolerance, reduce dyspnea, improve functional dependence, better HrQoL, prevent secondary pulmonary hypertension and RHF and improve survival for patients inresting or exertional hypoxaemia. LTOT is recommended for IPF patient with resting hypoxemia. LTOT is prescribed for atleast 15–18 hours per day in patients with resting hypoxemia. The impact of LTOT on breathlessness is also influenced by patient’s expectations. Despite being on LTOT many ILD patients experience anxiety because of social stigma and concerns that oxygen prescription is associate with end stage disease.
HFNO
It works with an air oxygen blender allowing from 21% to 100% fiO2, heating and humidifying the inspiratory gas and generating upto 60 L/min. HFNO causes favorable physiological effects, such as pharyngeal dead space washout, reduction of nasopharyngeal resistance, PEEP and reduction in airway resistance. HFNC may have a role in the management of CRF esp for end stage ILD patients and can be used as a palliative treatment. Compared with NIV, HFNC is associated with better tolerance, less temporary interruption and discontinuation rates, allowing patients to eat and converse just before death.
Non-invasive ventilation
NIV play a role in chronic setting in improving the quality of life in patients with end stage ILD.It also helps in hypercapnic respiratory failure and decreases daytime PaCO2 and increases PaO2. NIV plays a role as palliative treatment in end stage ILD along with supplemental oxygen, opoids. NIV has also been applied to ILD patients during rehabilitation programs. Patients benefit from NIV implementation to improve cardiopulmonary condition.
Palliative care
Palliative care is the active total care of patients whose disease is not responsive to curative treatment. Main goal of palliative care in ILD is to improve and maintain an acceptable quality of life during the end stage of disease.ILD clinical course is featured by a high burden of respiratory symptoms such as breathlessness and cough, accompanied in the advanced stages with fatigue, anxiety and depression. These symptoms if not controlled leads to severely impaired quality of life. Patients of end stage ILDs many a times lack access to palliation due to high variation in clinical course among different ILDs which makes it challenging to explain about the prognosis of the disease. For chronic lung diseases, such as COPD and fibrosing ILDs, it is necessary to identify the moment when the severity of the disease makes remissions rarer and shorter and causes anincrease in the number and duration of hospitalizations. LTOT prescription, age > 70 years, prior disease exacerbations, presence of “honeycomb” at HRCT and Usual Interstitial Pneumonia (UIP) histological pattern are associated with a poor prognosis and therefore may be considered as possible indicators for palliative care referral. Increased dependence in daily life activities and reduced functional autonomy, particularly when associated with higher degree of dyspnea, can also be considered useful indicators for palliative care initiation. Most used therapies for palliation include morphine and opioids, such as fentanyl, oxycodone and hydromorphone, in different administration forms (oral, subcutaneous, intravenous, transdermal etc). Similarto oncologic diseases, in the late phases of ILDs there is a strong need to provide access to adequate palliative care and discuss treatment and supportive options in a dedicated multidisciplinary setting in order to improve quality of life.
Rehabilitation
Pulmonary rehabilitation (PR) is defined by the ATS and ERS as a “comprehensive intervention based on a thorough patient assessment followed by patient-tailored therapies that include, but are not limited to, exercise training, educational and behavioural changes, designed to improve the physical and psychological condition of people with chronic respiratory disease and to promote the long-term adherence of health enhancing behaviours”. PR in ILD patients reduce dyspnoea, increase walking distance, increase maximum oxygen uptake and improve quality of life.PR has also been shown to reduce exertional dyspnoea in IPF patients as assessed by Borg scale, MRC and Chronic Respiratory Disease Questionnaire (CRDQ). The largest benefit following PR seems to occur in patients with asbestosis, followed by those with IPF, while patients with CTD-ILDs seem to receive less benefit from PR programs. The beneficial effects in ILDs, particularly in IPF, seem to be greater amongst patients with a shorter walking distance at baseline. Shorter (6-8 weeks) exercise training programs have been shown to improve symptoms and physical activity levels both during and after rehabilitation. Longer programs (3 months) seem able to maintain exercise oxygen uptake and lengthen constant load exercise time in patients with severe IPF. Successful adherence is more likely in patients with milder disease resulting in greater treatment effects. When adherence to the PR protocol is limited by severe dyspnea or fear of adverse events, an interval training approach may be useful. In CTD-ILDs, commonly associated with systemic manifestations such as joint pain and swelling, muscle weakness and pain, hydrotherapy or resistance training may be more suitable in achieving benefits.
Transplantation
Lung transplantation (LTx) can be a life-extending treatment option for patients with advanced and/or progressive fibrotic interstitial lung disease (ILD), especially idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, sarcoidosis and connective tissue disease-associated ILD. IPF is now the most common indication for LTx worldwide.
In IPF treatment guidelines by the American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT), LTx receives a strong recommendation based on a 75% reduced risk of death compared to medical management alone in well-selected patients, a survival benefit that probably also extends to patients with other severe or progressive ILDs. However, LTx in India is in its infancy and initial results have not been encouraging. As it is evolving, better protocols are being developed and it is likely to become available at many more centres. The challenge of organ availability needs a change in the social attitude and sensitization of public at large.
Obesity hypoventilation syndrome
Obesity hypoventilation syndrome (OHS) is defined as a combination of Obesity (BMI>40 kg/m2), daytime hypoventilation characterized by hypercapnia and hypoxemia (PaCO2 > 45 mm Hg and PaO2 < 70 mm Hg at sea level) and sleep-disordered breathing (SDB) in the absence of an alternative cause for hypoventilation like obstructive or restrictive lung disease, chest wall disorders like kyphoscoliosis, neuromuscular disorders and congenital central hypoventilation. The treatment for OHS is directed at the underlying pathophysiological factors contributing to hypoventilation. The management may be broadly divided into PAP therapy, weight loss induced by medical or surgical means and pharmacotherapy.
Positive airway pressure therapy
PAP therapy has been shown to improve daytime blood gases and quality of sleep. PAP therapy is usually in the form of continuous positive airway pressure (CPAP) therapy or non-invasive positive pressure ventilation (NIPPV) using a bi-level PAP or other advanced PAP modalities. Since majority of patients with OHS have OSA, CPAP therapy is recommended initially to improve nocturnal gas exchange by preventing obstructive apneas and hypopneas and reducing the work of breathing related to small airway closure and expiratory flow limitation. Following initiation of therapy over a period of few months, improvement in other physiological parameters such as gas exchange during wakefulness and ventilatory response to hypoxia and hypercapnia and also improvement in symptoms and health-related quality of life has been reported following use of CPAP in OHS.
Bi-level PAP should be strongly considered in patients who fail a CPAP trial, in OHS patients without OSA and in severe hypercapnic OHS where CPAP has not proven to be effective. Bi-level PAP therapy is beneficial in preventing obstructive events, improving expiratory flow limitation and also improves tidal volume by providing inspiratory pressure support. Bilevel therapy when used long term has been shown to improve blood gases, quality of life and ventilator responsiveness to CO2.Bi-level PAP therapy unloads inspiratory muscles and has been shown to reduce diaphragmatic effort by nearly 40%.
Bi-Level ventilators provide 3 different modes: (1) Spontaneous mode, in which each pressurization by the ventilator is triggered and cycled by the patient; (2) Spontaneous/timed (S/T) mode, in which, if the patient fails to initiate a pressurization within a time frame based on a back-up respiratory rate, the device will deliver a machine-triggered cycle for a defined inspiratory time; (3) Timed mode, in which the device delivers pressurizations at a preset respiratory rate, during a preset inspiratory time, without taking into account the patient’s inspiratory efforts. American Academy of Sleep Medicine (AASM) guidelines for the adjustment of NIPPV in chronic alveolar hypoventilation syndromes that were derived mostly from expert consensus recommended the spontaneous mode as the default setting, unless patients manifests a significant number of central apneas or a low spontaneous respiratory rate and are unable to trigger the ventilator . In the latter case a back-up respiratory rate was recommended. Newer PAP modalities like averaged volume-assured pressure support (AVAPS) combine the benefits of targeting minute ventilation and tidal volumes while delivering the comfort and advantages of pressure support ventilation making them ideal for patients with hypoventilation. These devices combine the technology of auto-PAP therapy to help determine optimal EPAP pressures. AVAPS may demonstrate better treatment adherence secondary to better patient-ventilator synchrony and lower median pressure support.
Hypoxia has been shown to be an independent predictor of mortality in OHS. Pulmonary arterial vasoconstriction secondary to hypoxia may cause pulmonary arterial hypertension but there appears to be significant inter-individual differences in such a response.
Withdrawal from positive airway pressure therapy has been shown to be associated with worsening nocturnal gas exchange in patients with chronic respiratory insufficiency related to restrictive thoracic disorders. The recovery of chemoreceptor secondary to improved gas exchange following NIPPV constitutes a very important factor in producing both clinical and functional improvements in patients with OHS. Based on the findings of long-term effects of NIPPV in OHS patients, NIPPV can be noted to improve lung function as evidenced by significant improvement in lung volumes, better gas exchange and is associated with reduced mortality. Moreover, NIPPV improves pulmonary hemodynamics and functional capacity in patients with comorbid pulmonary hypertension. The benefits of PAP on OHS are somewhat limited by poor adherence and intolerance in some patients.
Non-PAP treatment modalities in OHS
Non-PAP treatment options include exercise and rehabilitation, weight reduction, tracheostomy respiratory stimulants and oxygen therapy. Weight loss has been shown to improve lung function, respiratory muscle strength, and respiratory drive and sleep disordered breathing. Patients with BMI> 40 kg/m2 who have failed conservative management for weight loss or with BMI >35 kg/m2 who have obesity-related co-morbidities are candidates for bariatric surgery. Weight loss secondary to bariatric surgery has been shown to have a favorable outcome in terms of observed improvement of severity of sleep-disordered breathing, daytime and night time gas exchange, improved lung volumes and improved respiratory muscle strength. Sustained weight loss post-bariatric surgery has been shown to improve sleep apnea and OHS and can obviate the need for PAP therapy. Surgical weight loss provides additional metabolic effects such as better control of diabetes and hypertension and an overall reduction in mortality and morbidity.
Tracheostomy
Tracheostomy can reduce obstructive events associated with sleep-disordered breathing by bypassing the upper airway. Tracheostomy is currently limited to management of OHS when other options for treatment have failed.
Pharmacotherapy
Pharmacological agents that alter the ventilatory response to hypercapnia could be considered as adjuncts or alternatives to NIPPV. Acetazolamide, a carbonic anhydrase inhibitor, may stimulate ventilation by decreasing the serum bicarbonate and creating metabolic acidosis.
Medications such as fluticasone, Donepezil, paroxetine and combination of high dose ondansetron and fluoxetine showed improved from baseline AHI and subjective sleepiness during the day.
Exercise and Rehabilitation
Patients with OHS treated with NIPPV have been shown to improve their functional capacity (as measured by 6 minute walk test). It is thought that the improved nocturnal ventilation and daytime symptoms might be contributing to increased physical activity during the day.
Patients with OHS are likely to benefit from exercise and rehabilitation program.
Conclusion
Management of chronic respiratory failure needs a multipronged effort tailored to the needs of the individual patient. The aim is to improve symptomatology, QOL, prevent progression to the next level, development of complications like pulmonary hypertension or cor-pulmonale and life threatening episodes. Rehabilitation, mental health, nutrition and vaccination are the most neglected areas. High level of support, resources and motivation is required to manage these patients. Development of dedicated chronic respiratory failure facilities with the provision of multiple modalities under one roof can go a long term in managing this common but difficult condition.