Literature regarding the use of NIV for interstitial lung disease (ILD) is almost entirely populated by studies of hospitalized patients facing an initial or recurrent trial of intubation for acute-on-chronic respiratory failure and is beyond the scope of this review. However, an analysis of data from the Scleroderma Lung Study found that dyspnea severity was closely correlated with impairment of quality of life , which is also true for idiopathic pulmonary fibrosis (IPF) . The palliative application of NIV to ILD warrants future intellectual efforts.
Older studies of NIV used for chest wall and neuromuscular disorders (NMDs) are generally descriptive and include patients with various causes of ventilatory failure [16–19], some of which are rare [20,21]. More recent investigations of NIV have been observational in nature or controlled trials in which specific outcomes are evaluated in patients affected by a single disease, namely amyotrophic lateral sclerosis (ALS) [22,23,24▪▪,25] and Duchenne muscular dystrophy (DMD) [26,27▪▪,28]. Several well conducted studies [22,26,29,30] show that NIV improves survival in chest wall and NMDs. Some authors believe that future work in this field should try to explain global disparities in access to NIV [31▪▪].
Sometimes patients with chest wall and NMDs reach a point in their lives when they no longer wish to be supported by NIV. The healthcare provider has multiple obligations in this situation, not the least of which is discussing how the patient arrived at this conclusion and whether better managing symptoms by untried means is desirable. Autonomy should be validated whenever possible . Dialog around these issues should arguably start early in the disease course, but as Mitsumoto and Rabkin [45▪] highlight in their narrative about a neurologist with ALS, the healthcare provider must be sensitive to the patient's level of mental and physical readiness to withdraw some or all interventions that do not promote comfort. Simonds [2▪] aptly states that patients are often informed about ‘hard’ outcomes of various therapies, with little mention of their burdens. Interactive computer programs can help patients  and physicians  with advance care planning. Such ‘third-party’ tools might be able to defuse tensions between patient autonomy and physician paternalism.
In patients with solid tumors, respiratory failure, and limited life-expectancy, Nava et al.[67▪▪] recently evaluated the acceptability and effectiveness of NIV vs. oxygen in reducing dyspnea and opiate requirements. Randomization was stratified with respect to the presence or absence of hypercapnia (PaCO2 >45 mmHg). Subcutaneous morphine was administered to all patients to reduce breathlessness ratings by at least 1 point on the Borg scale. There were no significant baseline differences in demographic, physiologic, and prognostic parameters between the cohort of 99 patients treated with NIV and the cohort of 101 patients who received oxygen alone. The authors observed that dyspnea ratings fell more rapidly in the NIV group [mean reduction in Borg scale of 0.58, 95% confidence interval (CI) 0.23–0.92, P = 0.0012], especially in patients with hypercapnia. The average total morphine dose was 32.4 mg lower in NIV-treated patients through the first 48 h of treatment. Within the NIV group, survival at 3 and 6 months after discharge was higher among those with hypercapnia (hazard ratio = 0.41). The authors posited that NIV helped this subgroup overcome respiratory muscle fatigue and emphasized that only 11% of all NIV patients discontinued treatment. Azoulay et al. expressed concern that Nava et al.[67▪▪] combined patients with do-not-intubate orders who received NIV with curative intent and those who received NIV exclusively to alleviate dyspnea (i.e., comfort NIV). In their rebuttal, Nava et al. stated that all the study participants had voluntarily chosen to forego all life support, thus defining a single population of patients treated with comfort NIV.
Some concerns have been raised about the risks and limitations of NIV in patients with dyspnea and terminal cancer [72▪▪]. The first of these, whether NIV is prolonging life but not improving its quality, has an ethical basis. A dying patient might request NIV to buy enough time for a loved one to arrive at the bedside. However, clinicians would only appreciate this perspective if they take time to elicit their patient's expectations of NIV and, perhaps more importantly, to convey their opinions about whether NIV will or will not meet those expectations . Azad and Franco [72▪▪] have contended that a reduction in total morphine dose is an inappropriate endpoint for NIV research in cancer patients because this approach does not address variation in opiate responsiveness, tolerance, and susceptibility to side-effects. Secondly, results of single-center clinical trials could reflect institutional biases about the timing and location of NIV delivery, both of which probably contribute to heterogeneous NIV outcomes [74,75]. Finally, NIV can cause complications (see list below) that undermine its intended purpose as a palliative measure . Complications associated with NIV are as follows:
Papers of particular interest, published within the annual period of review, have been highlighted as:
1. Hess DR. Noninvasive ventilation
in neuromuscular disease: equipment and application. Respir Care 2006; 51:896–911.
2▪. Simonds AK. Ethics and decision making in end stage lung disease. Thorax 2003; 58:272–277.
An excellent discussion of the ethical considerations in the use of NIV which emphasizes decision-making principles.
3. Mahler DA. Mechanisms and measurement of dyspnea
in chronic obstructive pulmonary disease
. Proc Am Thorac Soc 2006; 3:234–238.
4. Lightowler JV, Wedzicha JA, Elliott MW, Ram FS. Noninvasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease
: Cochrane systematic review and meta-analysis. BMJ 2003; 326:185.
5▪. Tuggey JM, Plant PK, Elliott MW. Domiciliary noninvasive ventilation
for recurrent acidotic exacerbations of COPD: an economic analysis. Thorax 2003; 58:867–871.
This is the only published study to provide detailed cost estimates associated with home NIV use by COPD patients.
6. Dreher M, Storre JH, Schmoor C, Windisch W. High-intensity versus low-intensity noninvasive ventilation
in patients with stable hypercapnic COPD: a randomised crossover trial. Thorax 2010; 65:303–308.
7. Duiverman ML, Wempe JB, Bladder G, et al. Nocturnal noninvasive ventilation
in addition to rehabilitation in hypercapnic patients with COPD. Thorax 2008; 63:1052–1057.
8. McEvoy RD, Pierce RJ, Hillman D, et al. Nocturnal noninvasive nasal ventilation in stable hypercapnic COPD: a randomised controlled trial. Thorax 2009; 64:561–566.
9. Tsolaki V, Pastaka C, Karetsi E, et al. One-year noninvasive ventilation
in chronic hypercapnic COPD: effect on quality of life. Respir Med 2008; 102:904–911.
10. Windisch W. Impact of home mechanical ventilation on health-related quality of life. Eur Respir J 2008; 32:1328–1336.
11. Moran F, Bradley JM, Piper AJ. Noninvasive ventilation
for cystic fibrosis. Cochrane Database Syst Rev 2013; 4:CD002769.
12. Young AC, Wilson JW, Kotsimbos TC, Naughton MT. Randomised placebo controlled trial of noninvasive ventilation
for hypercapnia in cystic fibrosis. Thorax 2008; 63:72–77.
13. Gozal D. Nocturnal ventilatory support in patients with cystic fibrosis: comparison with supplemental oxygen. Eur Respir J 1997; 10:1999–2003.
14. Khanna D, Clements PJ, Furst DE, et al. Correlation of the degree of dyspnea
with health-related quality of life, functional abilities, and diffusing capacity for carbon monoxide in patients with systemic sclerosis and active alveolitis: results from the Scleroderma Lung Study. Arthritis Rheum 2005; 52:592–600.
15. Nishiyama O, Taniguchi H, Kondoh Y, et al. Health-related quality of life in patients with idiopathic pulmonary fibrosis. What is the main contributing factor? Respir Med 2005; 99:408–414.
16. Baydur A, Layne E, Aral H, et al. Long term noninvasive ventilation
in the community for patients with musculoskeletal disorders: 46 year experience and review. Thorax 2000; 55:4–11.
17. Katz S, Selvadurai H, Keilty K, et al. Outcome of noninvasive positive pressure ventilation in paediatric neuromuscular disease. Arch Dis Child 2004; 89:121–124.
18. Heckmatt JZ, Loh L, Dubowitz V. Night-time nasal ventilation in neuromuscular disease. Lancet 1990; 335:579–582.
19. Mellies U, Ragette R, Dohna Schwake C, et al. Long-term noninvasive ventilation
in children and adolescents with neuromuscular disorders. Eur Res J 2003; 22:631–636.
20. Jackson M, Smith I, King M, Shneerson J. Long term noninvasive domiciliary assisted ventilation for respiratory failure following thoracoplasty. Thorax 1994; 49:915–919.
21. Smyth A, Riley M. Chronic respiratory failure: an unusual cause and treatment. Thorax 2002; 57:835–836.
22. Bourke SC, Tomlinson M, Williams TL, et al. Effects of noninvasive ventilation
on survival and quality of life in patients with amyotrophic lateral sclerosis
: a randomised controlled trial. Lancet Neurol 2006; 5:140–147.
23. Mustfa N, Walsh E, Bryant V, et al. The effect of noninvasive ventilation
on ALS patients and their caregivers. Neurology 2006; 66:1211–1217.
24▪▪. Siirala W, Aantaa R, Olkkola KT, et al. Is the effect of noninvasive ventilation
on survival in amyotrophic lateral sclerosis
age-dependent? retrospective cohort study. BMC Palliat Care 2013; 12:23.
This registry-based study showed that NIV improved mortality in ALS patients at least 65 years old, although data on quality of life were not presented.
25. Mahajan KR, Bach JR, Saporito L, Perez N. Diaphragm pacing and noninvasive respiratory management of amyotrophic lateral sclerosis
/motor neuron disease. Muscle Nerve 2012; 46:851–855.
26. Bach JR, Martinez D. Duchenne muscular dystrophy: continuous noninvasive ventilatory support prolongs survival. Respir Care 2011; 56:744–750.
27▪▪. McKim DA, Griller N, LeBlanc C, et al. Twenty-four hour noninvasive ventilation
in Duchenne muscular dystrophy: a safe alternative to tracheostomy. Can Respir J 2013; 20:e5–e9.
Around-the-clock NIV delivered by mask at night and mouthpiece during the day was tolerated by a small cohort of patients with DMD. On the basis of this finding, the authors concluded that continuous NIV is a possible alternative to tracheostomy in this disease.
28. Toussaint M, Soudon P, Kinnear W. Effect of noninvasive ventilation
on respiratory muscle loading and endurance in patients with Duchenne muscular dystrophy. Thorax 2008; 63:430–434.
29. Jackson CE, Rosenfeld J, Moore DH, et al. A preliminary evaluation of a prospective study of pulmonary function studies and symptoms of hypoventilation in ALS/MND patients. J Neurol Sci 2001; 191:75–78.
30. Lechtzin N, Scott Y, Busse AM, et al. Early use of noninvasive ventilation
prolongs survival in subjects with ALS. Amyotroph Lateral Scler 2007; 8:185–188.
31▪▪. Radunovic A, Annane D, Rafiq MK, Mustfa N. Mechanical ventilation for amyotrophic lateral sclerosis
/motor neuron disease. Cochrane Database Syst Rev 2013; 3:CD004427.
These authors call for further study of the health economics of NIV, including personal and socioeconomic factors associated limited access to this intervention.
32. Manning HL, Schwartzstein RM. Pathophysiology of dyspnea
. N Engl J Med 1995; 333:1547–1553.
33. Lanini B, Misuri G, Gigliotti F, et al. Perception of dyspnea
in patients with neuromuscular disease. Chest 2001; 120:402–408.
34. Clague JE, Carter J, Coakley J, et al. Respiratory effort perception at rest and during carbon dioxide rebreathing in patients with dystrophia myotonica. Thorax 1994; 49:240–244.
35. Bourke SC, Gibson GJ. Sleep and breathing in neuromuscular disease. Eur Respir J 2002; 19:1194–1201.
36. Mellies U, Ragette R, Schwake C, et al. Daytime predictors of sleep disordered breathing in children and adolescents with neuromuscular disorders. Neuromuscul Disord 2003; 13:123–128.
37. Atalaia A, De Carvalho M, Evangelista T, Pinto A. Sleep characteristics of amyotrophic lateral sclerosis
in patients with preserved diaphragmatic function. Amyotroph Lateral Scler 2007; 8:101–105.
38. Ward S, Chatwin M, Heather S, Simonds AK. Randomised controlled trial of noninvasive ventilation
(NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia. Thorax 2005; 60:1019–1024.
39▪. Elman LB, Siderowf AD, McCluskey LF. Nocturnal oximetry: utility in the respiratory management of amyotrophic lateral sclerosis
. Am J Phys Med Rehabil 2003; 82:866–870.
This study demonstrated that many ALS patients with a forced vital capacity (FVC) greater than 50% experience clinically significant overnight oxyhemoglobin desaturation. The authors conclude that this FVC criterion is not appropriate to determine whether NIV should be instituted; rather, overnight oximetry is probably more helpful.
40. Miller RG, Jackson CE, Kasarskis EJ, et al. Practice parameter update: the care of the patient with amyotrophic lateral sclerosis
: multidisciplinary care, symptom management, and cognitive/behavioral impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2009; 73:1227–1233.
41. David WS, Bundlie SR, Mahdavi Z. Polysomnographic studies in amyotrophic lateral sclerosis
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42. Newsom-Davis IC, Lyall RA, Leigh PN, et al. The effect of noninvasive positive pressure ventilation (NIPPV) on cognitive function in amyotrophic lateral sclerosis
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43. Aboussouan LS, Khan SU, Banerjee M, et al. Objective measures of the efficacy of noninvasive positive-pressure ventilation in amyotrophic lateral sclerosis
. Muscle Nerve 2001; 24:403–409.
44. Andersen PM, Borasio GD, Dengler R, et al. EFNS task force on management of amyotrophic lateral sclerosis
: guidelines for diagnosing and clinical care of patients and relatives. Eur J Neurol 2005; 12:921–938.
45▪. Mitsumoto H, Rabkin JG. Palliative care for patients with amyotrophic lateral sclerosis
: ‘prepare for the worst and hope for the best’. JAMA 2007; 298:207–216.
A poignant reflection on the personal journey of a neurologist who developed ALS.
46. Hossler C, Levi BH, Simmons Z, Green MJ. Advance care planning for patients with ALS: feasibility of an interactive computer program. Amyotroph Lateral Scler 2011; 12:172–177.
47. Levi BH, Heverley SR, Green MJ. Accuracy of a decision aid for advance care planning: simulated end-of-life decision making. J Clin Ethics 2011; 22:223–238.
48▪▪. Schnell D, Mayaux J, Lambert J, et al. Clinical assessment for identifying causes of acute respiratory failure in cancer
patients. Eur Respir J 2013; 42:435–443.
This study refines our understanding of respiratory failure in cancer patients who are admitted to the ICU. Some of these processes would be expected to respond better than others to NIV. These insights may inform future clinical trials of NIV in this population.
49. Meert AP, Close L, Hardy M, et al. Noninvasive ventilation
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50. Azoulay E, Mokart D, Lambert J, et al. Diagnostic strategy for hematology and oncology patients with acute respiratory failure: randomized controlled trial. Am J Respir Crit Care Med 2010; 182:1038–1046.
51. Zhang Y, Yang H, Zhao M, He J. Successful treatment of gefitinib-induced acute interstitial pneumonitis with corticosteroid and noninvasive BIPAP-ventilation. J Thorac Dis 2012; 4:316–319.
52. Cogliati AA, Conti G, Tritapepe L, et al. Noninvasive ventilation
in the treatment of acute respiratory failure induced by all-trans retinoic acid (retinoic acid syndrome) in children with acute promyelocytic leukemia. Pediatr Crit Care Med 2002; 3:70–73.
53. Bassani MA, de Oliveira AB, Oliveira Neto AF. Noninvasive ventilation
in a pregnant patient with respiratory failure from all-trans-retinoic-acid (ATRA) syndrome. Respir Care 2009; 54:969–972.
54. Briasoulis E, Froudarakis M, Milionis HJ, et al. Chemotherapy-induced noncardiogenic pulmonary edema related to gemcitabine plus docetaxel combination with granulocyte colony-stimulating factor support. Respiration 2000; 67:680–683.
55. Levy M, Tanios MA, Nelson D, et al. Outcomes of patients with do-not-intubate orders treated with noninvasive ventilation
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56. Nava S, Hill N. Noninvasive ventilation
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57. Pene F, Aubron C, Azoulay E, et al. Outcome of critically ill allogeneic hematopoietic stem-cell transplantation recipients: a reappraisal of indications for organ failure supports. J Clin Oncol 2006; 24:643–649.
58. Pene F, Percheron S, Lemiale V, et al. Temporal changes in management and outcome of septic shock in patients with malignancies in the intensive care unit. Crit Care Med 2008; 36:690–696.
59. Adam AK, Soubani AO. Outcome and prognostic factors of lung cancer
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60. Azoulay E, Alberti C, Bornstain C, et al. Improved survival in cancer
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61. Azoulay E, Soares M, Darmon M, et al. Intensive care of the cancer
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62. Cuomo A, Delmastro M, Ceriana P, et al. Noninvasive mechanical ventilation as a palliative treatment of acute respiratory failure in patients with end-stage solid cancer
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63. Schettino G, Altobelli N, Kacmarek RM. Noninvasive positive pressure ventilation reverses acute respiratory failure in select ‘do-not-intubate’ patients. Crit Care Med 2005; 33:1976–1982.
64▪. Depuydt PO, Benoit DD, Roosens CD, et al. The impact of the initial ventilatory strategy on survival in hematological patients with acute hypoxemic respiratory failure. J Crit Care 2010; 25:30–36.
In this study of patients with hematologic malignancies complicated by severe hypoxic respiratory failure, NIV use within 24 h of ICU admission, compared with invasive positive pressure ventilation and supplemental oxygen, did not confer better outcomes.
65. Hampshire PA, Welch CA, McCrossan LA, et al. Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database. Crit Care 2009; 13:R137.
66. Curtis JR, Cook DJ, Sinuff T, et al. Noninvasive positive pressure ventilation in critical and palliative care settings: understanding the goals of therapy. Crit Care Med 2007; 35:932–939.
67▪▪. Nava S, Ferrer M, Esquinas A, et al. Palliative use of noninvasive ventilation
in end-of-life patients with solid tumours: a randomised feasibility trial. Lancet Oncol 2013; 14:219–227.
This multicenter, randomized controlled trial investigated the feasibility of NIV as a palliative measure compared to oxygen in terminally ill patients with solid tumors and distress from acute respiratory failure. The effect of NIV on total morphine dose necessary to reduce dyspnea using the Borg scale was presented as a novel endpoint.
68. Azoulay E, Kouatchet A, Jaber S, et al. Noninvasive ventilation
for end-of-life oncology patients. Lancet Oncol 2013; 14:e200–e201.
69. Fadul NA, El Osta B, Dalal S, et al. Comparison of symptom burden among patients referred to palliative care with hematologic malignancies versus those with solid tumors. J Palliat Med 2008; 11:422–427.
70. Piastra M, Antonelli M, Chiaretti A, et al. Treatment of acute respiratory failure by helmet-delivered noninvasive pressure support ventilation in children with acute leukemia: a pilot study. Intensive Care Med 2004; 30:472–476.
71. Depuydt PO, Benoit DD, Vandewoude KH, et al. Outcome in noninvasively and invasively ventilated hematologic patients with acute respiratory failure. Chest 2004; 126:1299–1306.
72▪▪. Azad A, Franco M. Noninvasive ventilation
for end-of-life oncology patients. Lancet Oncol 2013; 14:e199–e200.
These authors contend that because Nava et al.[67▪▪] excluded patients if opioids had been used within 2 weeks of enrollment, the study has limited generalizability. Azad and Franco also point out that only hypercarbic patients derived benefit from NIV.
73. Kacmarek RM. Should noninvasive ventilation
be used with the do-not-intubate patient? Respir Care 2009; 54:223–229.
74. Squadrone V, Massaia M, Bruno B, et al. Early CPAP prevents evolution of acute lung injury in patients with hematologic malignancy. Intensive Care Med 2010; 36:1666–1674.
75. Wermke M, Schiemanck S, Hoffken G, et al. Respiratory failure in patients undergoing allogeneic hematopoietic SCT – a randomized trial on early noninvasive ventilation
based on standard care hematology wards. Bone Marrow Transplant 2012; 47:574–580.
76. Gay PC. Complications of noninvasive ventilation
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