Comment
that the MUC5B and TOLLIP gene loci are separated by a recombination hotspot and are independent. They present expression data showing downregulation of TOLLIP expression in lung tissues from patients with IPF carrying the identified SNPs. Additionally, they report modest support from regression analysis for significance of the TOLLIP gene signal (p=0·05 for all three SNPs) in a model that accounted for the MUC5B association. However, several independent signals from a regional locus are commonplace in complex diseases and their existence here is therefore not remarkable. Both genes are plausible candidates for disease and neither is actually proven beyond some other gene or non-coding, regional variation affecting local gene expression. Occam’s razor would posit the simplest theory that one causal locus lies within this discrete genomic region of chromosome 11 and that higher-order complexity should not be assumed without additional persuasive evidence that explains more of the data. Either way, Noth and colleagues’ report5 adds substantial independent weight to the importance of chromosome 11p in IPF susceptibility and will undoubtedly stimulate additional research to assess the functional effect of local variation. This research is urgently needed to resolve the
biological pathways underpinning susceptibility, because clarity about the precise nature of mutation in the region should aid prediction and diagnosis, and provide novel therapeutic targets for this devastating disease. Sarah Ennis Human Genetics and Genomic Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK [email protected] I declare that I have no conflicts of interest. 1
2
3 4 5
6 7
Spagnolo P, Tonelli R, Cocconcelli E, et al. Idiopathic pulmonary fibrosis: diagnostic pitfalls and therapeutic challenges. Multidiscip Respir Med 2012; 7: 42. García-Sancho C, Buendía-Roldán I, Fernández-Plata MR, et al. Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis. Respir Med 2011; 105: 1902–07. Kropski JA, Lawson WE, Young LR, et al. Genetic studies provide clues on the pathogenesis of idiopathic pulmonary fibrosis. Dis Model Mech 2013; 6: 9–17. Seibold MA, Wise AL, Speer MC, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 2011; 364: 1503–12. Noth I, Zhang Y, Ma S-F, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med 2013; published online April 17. http://dx.doi. org/10.1016/S2213-2600(13)70045-6. Hoggart CJ, Clark TG, De IM, et al. Genome-wide significance for dense SNP and resequencing data. Genet Epidemiol 2008; 32: 179–85. Shah JA, Vary JC, Chau TT, et al. Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis. J Immunol 2012; 189: 1737–46.
Palliative care—ie, the provision of comfort measures to patients with life-threatening or end-stage disease— should be the rule, not the exception. Medical care given to patients in the 21st century is advanced. Pharmaceutical companies use new techniques to develop drugs that are tailored to specific diseases. Likewise, surgical interventions involving robotics and laser technologies are used in intricate procedures, which save lives. Unfortunately, at the end of life when all reasonable curative interventions have failed, many patients with end-stage lung disease still die in pain after much suffering. Palliative care is not a new idea or notion. As defined in the 1970s,1 palliative care is physical, social, psychological, and spiritual support given to patients with a life-limiting illness by a multidisciplinary team. It has no downside; there are no age limits, time constraints, or barriers to therapeutic interventions. However, palliative care does demand commitment from health-care providers and the ability to change course as the patient’s condition www.thelancet.com/respiratory Vol 1 June 2013
changes or their priorities shift.2 The only intangible barriers to good end-of-life care seem to be awareness and knowledge. In most institutions, patients with terminal cancer receive interventions that adequately control symptoms. Patients with other chronic life-threatening diseases, such as advanced pulmonary disease, often do not receive care to manage their symptoms until late in the course of treatment. Understandably, an estimation of poor survival in patients with aggressive cancer might be more predictable than in patients with other end-stage diseases, but that should not preclude the provision of palliative care to all patients in need of symptom control. In 2012, a report3 made a clear case for early palliative care in patients with chronic obstructive pulmonary disease (COPD). Why is it such a challenge? Why are troublesome symptoms in patients with advanced COPD not alleviated on a regular basis? Part of the answer relates to perceived barriers to palliative care, which can be separated into different types of factors
BSIP, MAY/Science Photo Library
Palliative care for lung disease: start early, stay late
Published Online May 17, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70083-3
279
Comment
(panel).4 However, these factors should not be viewed as circumstances that are beyond control. Hospice care is clearly defined (less than 6 months to live, as established by a physician) and understood by most adults, but palliative care, which has no time constraints, is often misunderstood and presumed by many to be synonymous with hospice care. When patients correlate hospice with death, and presume hospice and palliative care are the same or similar, they might be resistant to finding out what palliative care services have to offer. Therefore, the difference needs to be better explained to patients. Both hospice and palliative care are integral to care of the dying patient. Even though palliative care is associated with improved outcomes for patients and families,5 it is underused. Early palliative care improves quality of life and extends survival in patients with non-small-cell lung cancer,6 yet has not become a standard of care for patients with endstage pulmonary disease. Early palliative interventions can make a great difference in quality of life, when quantity of life is going to be shortened by disease. Pistoria7 outlined the results of research into end-oflife decisions made by physicians. In a survey of almost 800 physicians, nearly 90% would not want to receive cardiopulmonary resuscitation if they were in a chronic coma, compared with only 25% of members of the public who would not desire so-called heroic measures.7 Physicians know about the likelihood of success and outcomes of various resuscitative interventions, but patients and families do not fully understand the potential results of decisions that they make about end-of-life care. Given accurate information about the expected course of disease and options for care in a timely manner, patients with pulmonary disease might respond unexpectedly. They might choose comfort over pain, rehabilitation over the sofa, and home over the intensive care unit.
Panel: Perceived barriers to palliative care in chronic obstructive pulmonary disorder4 Patient factors • Unwillingness to discuss end of life • Poor understanding of palliative-care principles • Communication issues or language barriers Physician factors • Uncertainty about prognosis • Scarce resources or time constraints • Poor understanding of palliative-care principles • Commitment to preserve life at all costs Therapist factors • Poor understanding of palliative-care principles • No palliative care order in chart • Fear of reprisal by physician or supervisor
Health-care professionals need to start educating about the goals of palliative care early at the same time as providing appropriate curative care, to give patients with lung disease the very best that can be offered. Helen M Sorenson University of Texas Health Science Center, San Antonio, TX 78229–3900, USA [email protected] I declare that I have no conflicts of interest. 1 2 3 4 5 6 7
Clark D. From margins to centre: a review of the history of palliative care in cancer. Lancet Oncol 2007; 8: 430–38. Byock I. The best care possible: a physician’s quest to transform care through the end of life. New York, NY: Penguin, 2012. Carlucci A, Guerrieri A, Nava S. Palliative care in COPD patients: is it only an end-of-life issue? Eur Respir Rev 2012; 21: 346–54. Spence A, Hasson F, Waldron M, et al. Professionals delivering palliative care to people with COPD: a qualitative study. Palliat Med 2009; 23: 126–31. Litrivis E, Smith CB. Palliative care: a primer. Mt Sinai J Med 2011; 78: 627–31. Temel JS, Greer JA, Muzikansky MA, et al. Early palliative care for patients with metastatic non-small cell lung cancer. N Engl J Med 2010; 363: 733–42. Pistoria MJ. Why should doctors die differently? March, 2013. http://www. nxtbook.com/nxtbooks/elsevier/chest_201303/index.php?startid=4 (accessed May 3, 2013).
Neonatal respiratory care: not how, but where and when See News page 288
280
In 1963, US President John F Kennedy’s son Patrick was born at 34 weeks’ gestation with a birth weight of 2100 g. He died 3 days later from complications of hyaline membrane disease. At the time, treatment of newborn babies with respiratory distress was limited to supplemental oxygen. In the next 30 years, neonatology was revolutionised by the introduction of antenatal
corticosteroids to enhance fetal lung maturation, continuous positive airway pressure, invasive mechanical ventilation, and surfactant replacement therapy. By the early 1990s, survival had become the expected outcome for most infants with hyaline membrane disease, and the limit of viability had reached 24 weeks. Although mortality of premature infants was decreasing, www.thelancet.com/respiratory Vol 1 June 2013
that the MUC5B and TOLLIP gene loci are separated by a recombination hotspot and are independent. They present expression data showing downregulation of TOLLIP expression in lung tissues from patients with IPF carrying the identified SNPs. Additionally, they report modest support from regression analysis for significance of the TOLLIP gene signal (p=0·05 for all three SNPs) in a model that accounted for the MUC5B association. However, several independent signals from a regional locus are commonplace in complex diseases and their existence here is therefore not remarkable. Both genes are plausible candidates for disease and neither is actually proven beyond some other gene or non-coding, regional variation affecting local gene expression. Occam’s razor would posit the simplest theory that one causal locus lies within this discrete genomic region of chromosome 11 and that higher-order complexity should not be assumed without additional persuasive evidence that explains more of the data. Either way, Noth and colleagues’ report5 adds substantial independent weight to the importance of chromosome 11p in IPF susceptibility and will undoubtedly stimulate additional research to assess the functional effect of local variation. This research is urgently needed to resolve the
biological pathways underpinning susceptibility, because clarity about the precise nature of mutation in the region should aid prediction and diagnosis, and provide novel therapeutic targets for this devastating disease. Sarah Ennis Human Genetics and Genomic Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK [email protected] I declare that I have no conflicts of interest. 1
2
3 4 5
6 7
Spagnolo P, Tonelli R, Cocconcelli E, et al. Idiopathic pulmonary fibrosis: diagnostic pitfalls and therapeutic challenges. Multidiscip Respir Med 2012; 7: 42. García-Sancho C, Buendía-Roldán I, Fernández-Plata MR, et al. Familial pulmonary fibrosis is the strongest risk factor for idiopathic pulmonary fibrosis. Respir Med 2011; 105: 1902–07. Kropski JA, Lawson WE, Young LR, et al. Genetic studies provide clues on the pathogenesis of idiopathic pulmonary fibrosis. Dis Model Mech 2013; 6: 9–17. Seibold MA, Wise AL, Speer MC, et al. A common MUC5B promoter polymorphism and pulmonary fibrosis. N Engl J Med 2011; 364: 1503–12. Noth I, Zhang Y, Ma S-F, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med 2013; published online April 17. http://dx.doi. org/10.1016/S2213-2600(13)70045-6. Hoggart CJ, Clark TG, De IM, et al. Genome-wide significance for dense SNP and resequencing data. Genet Epidemiol 2008; 32: 179–85. Shah JA, Vary JC, Chau TT, et al. Human TOLLIP regulates TLR2 and TLR4 signaling and its polymorphisms are associated with susceptibility to tuberculosis. J Immunol 2012; 189: 1737–46.
Palliative care—ie, the provision of comfort measures to patients with life-threatening or end-stage disease— should be the rule, not the exception. Medical care given to patients in the 21st century is advanced. Pharmaceutical companies use new techniques to develop drugs that are tailored to specific diseases. Likewise, surgical interventions involving robotics and laser technologies are used in intricate procedures, which save lives. Unfortunately, at the end of life when all reasonable curative interventions have failed, many patients with end-stage lung disease still die in pain after much suffering. Palliative care is not a new idea or notion. As defined in the 1970s,1 palliative care is physical, social, psychological, and spiritual support given to patients with a life-limiting illness by a multidisciplinary team. It has no downside; there are no age limits, time constraints, or barriers to therapeutic interventions. However, palliative care does demand commitment from health-care providers and the ability to change course as the patient’s condition www.thelancet.com/respiratory Vol 1 June 2013
changes or their priorities shift.2 The only intangible barriers to good end-of-life care seem to be awareness and knowledge. In most institutions, patients with terminal cancer receive interventions that adequately control symptoms. Patients with other chronic life-threatening diseases, such as advanced pulmonary disease, often do not receive care to manage their symptoms until late in the course of treatment. Understandably, an estimation of poor survival in patients with aggressive cancer might be more predictable than in patients with other end-stage diseases, but that should not preclude the provision of palliative care to all patients in need of symptom control. In 2012, a report3 made a clear case for early palliative care in patients with chronic obstructive pulmonary disease (COPD). Why is it such a challenge? Why are troublesome symptoms in patients with advanced COPD not alleviated on a regular basis? Part of the answer relates to perceived barriers to palliative care, which can be separated into different types of factors
BSIP, MAY/Science Photo Library
Palliative care for lung disease: start early, stay late
Published Online May 17, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70083-3
279
Comment
(panel).4 However, these factors should not be viewed as circumstances that are beyond control. Hospice care is clearly defined (less than 6 months to live, as established by a physician) and understood by most adults, but palliative care, which has no time constraints, is often misunderstood and presumed by many to be synonymous with hospice care. When patients correlate hospice with death, and presume hospice and palliative care are the same or similar, they might be resistant to finding out what palliative care services have to offer. Therefore, the difference needs to be better explained to patients. Both hospice and palliative care are integral to care of the dying patient. Even though palliative care is associated with improved outcomes for patients and families,5 it is underused. Early palliative care improves quality of life and extends survival in patients with non-small-cell lung cancer,6 yet has not become a standard of care for patients with endstage pulmonary disease. Early palliative interventions can make a great difference in quality of life, when quantity of life is going to be shortened by disease. Pistoria7 outlined the results of research into end-oflife decisions made by physicians. In a survey of almost 800 physicians, nearly 90% would not want to receive cardiopulmonary resuscitation if they were in a chronic coma, compared with only 25% of members of the public who would not desire so-called heroic measures.7 Physicians know about the likelihood of success and outcomes of various resuscitative interventions, but patients and families do not fully understand the potential results of decisions that they make about end-of-life care. Given accurate information about the expected course of disease and options for care in a timely manner, patients with pulmonary disease might respond unexpectedly. They might choose comfort over pain, rehabilitation over the sofa, and home over the intensive care unit.
Panel: Perceived barriers to palliative care in chronic obstructive pulmonary disorder4 Patient factors • Unwillingness to discuss end of life • Poor understanding of palliative-care principles • Communication issues or language barriers Physician factors • Uncertainty about prognosis • Scarce resources or time constraints • Poor understanding of palliative-care principles • Commitment to preserve life at all costs Therapist factors • Poor understanding of palliative-care principles • No palliative care order in chart • Fear of reprisal by physician or supervisor
Health-care professionals need to start educating about the goals of palliative care early at the same time as providing appropriate curative care, to give patients with lung disease the very best that can be offered. Helen M Sorenson University of Texas Health Science Center, San Antonio, TX 78229–3900, USA [email protected] I declare that I have no conflicts of interest. 1 2 3 4 5 6 7
Clark D. From margins to centre: a review of the history of palliative care in cancer. Lancet Oncol 2007; 8: 430–38. Byock I. The best care possible: a physician’s quest to transform care through the end of life. New York, NY: Penguin, 2012. Carlucci A, Guerrieri A, Nava S. Palliative care in COPD patients: is it only an end-of-life issue? Eur Respir Rev 2012; 21: 346–54. Spence A, Hasson F, Waldron M, et al. Professionals delivering palliative care to people with COPD: a qualitative study. Palliat Med 2009; 23: 126–31. Litrivis E, Smith CB. Palliative care: a primer. Mt Sinai J Med 2011; 78: 627–31. Temel JS, Greer JA, Muzikansky MA, et al. Early palliative care for patients with metastatic non-small cell lung cancer. N Engl J Med 2010; 363: 733–42. Pistoria MJ. Why should doctors die differently? March, 2013. http://www. nxtbook.com/nxtbooks/elsevier/chest_201303/index.php?startid=4 (accessed May 3, 2013).
Neonatal respiratory care: not how, but where and when See News page 288
280
In 1963, US President John F Kennedy’s son Patrick was born at 34 weeks’ gestation with a birth weight of 2100 g. He died 3 days later from complications of hyaline membrane disease. At the time, treatment of newborn babies with respiratory distress was limited to supplemental oxygen. In the next 30 years, neonatology was revolutionised by the introduction of antenatal
corticosteroids to enhance fetal lung maturation, continuous positive airway pressure, invasive mechanical ventilation, and surfactant replacement therapy. By the early 1990s, survival had become the expected outcome for most infants with hyaline membrane disease, and the limit of viability had reached 24 weeks. Although mortality of premature infants was decreasing, www.thelancet.com/respiratory Vol 1 June 2013
