The application of in vivo genetic lineage tracing has advanced our understanding of cellular mechanisms for tissue renewal in organs with slow turnover, like the lung. These studies have identified an adult stem cell with very different properties than classically understood ones that maintain continuously cycling tissues such as the intestine. A portrait has emerged of an ensemble of cellular programs that replenish the cells that line the gas exchange (alveolar) surface, enabling a response tailored to the extent of cell (...) loss. A capacity for differentiated cells to undergo direct lineage transitions allows for local restoration of proper cell balance at sites of injury. We present these recent findings as a paradigm for how a relatively quiescent tissue compartment can maintain homeostasis throughout a lifetime punctuated by injuries ranging from mild to life‐threatening, and discuss how dysfunction or insufficiency of alveolar repair programs produce serious health consequences like cancer and fibrosis. (shrink)

Richard, a sixty‐seven‐year‐old man, has been admitted to Midtown University Center for difficulty breathing. He has a significant medical history that includes pulmonary fibrosis and subsequent heart failure, and he depends on supplemental oxygen to breathe. Upon admission and after discussing his prognosis with his family and doctors, Richard decided to sign a do‐not‐resuscitate order stating that if his heart stops or he stops breathing, he does not want to undergo cardiopulmonary resuscitation or other life‐sustaining measures. On his (...) third day in the hospital, the nurse practitioner who is caring for Richard notices that his breathing is becoming more labored and that his blood pressure is steadily dropping. She thinks he requires closer observation and treatment in the cardiac intensive care unit. Dr. P, the physician in the intensive care unit at the time, Dr. P does not want to accept Richard into the CICU because of his prognosis and his DNR order. He believes that Richard should be cared for on a regular hospital floor, and that the last bed in the CICU should be held for its intended user—a patient suffering a life‐threatening heart attack who requires intensive care. Should Richard be admitted to the CICU? (shrink)

Richard, a sixty‐seven‐year‐old man, has been admitted to Midtown University Center for difficulty breathing. He has a significant medical history that includes pulmonary fibrosis and subsequent heart failure, and he depends on supplemental oxygen to breathe. Upon admission and after discussing his prognosis with his family and doctors, Richard decided to sign a do‐not‐resuscitate order stating that if his heart stops or he stops breathing, he does not want to undergo cardiopulmonary resuscitation or other life‐sustaining measures. On his (...) third day in the hospital, the nurse practitioner who is caring for Richard notices that his breathing is becoming more labored and that his blood pressure is steadily dropping. She thinks he requires closer observation and treatment in the cardiac intensive care unit. Dr. P, the physician in the intensive care unit at the time, Dr. P does not want to accept Richard into the CICU because of his prognosis and his DNR order. He believes that Richard should be cared for on a regular hospital floor, and that the last bed in the CICU should be held for its intended user—a patient suffering a life‐threatening heart attack who requires intensive care. Should Richard be admitted to the CICU? (shrink)

At present, in the UK, live lobe donation of the lung is generally considered in the context of patients with cystic fibrosis (CF) which is a life-threatening, inherited disease.1 However, if this technique is successfully developed it may be applicable to other patients with end stage lung disease. Cystic fibrosis is a disease where the major morbidity and mortality is due to pulmonary infection and respiratory failure.2 In l938 70% of patients born with CF died within one (...) year of birth, but now the average survival has improved to 32 years.1 The improved survival has been due to improved medical care, but also, and in very large measure, to the devotion of the families who have carried out time-consuming daily treatments such as chest physiotherapy, nebuliser treatment, high calorie diets etc. To these patients and their families lung transplantation brought new hope.3 The first successful transplant for CF was performed in the UK in 1985 and we now have patients alive and well more than ten years after transplantation. However, sadly, nearly 50% of patients with CF die on the transplant waiting list because of a shortage of donor organs from brain stem dead donors. This is a tragedy for the individual patient, the families and those who care for them. Is there a way forward? Education of the public so that a relative of a brain dead individual will give permission for the organs to be used has been carried out for many years but only with a small increase in the number of available organs. “Required request” where doctors would be required, by law, to ask relatives of brain dead patients to consider transplantation and “assume consent” where consent to donation is assumed unless there is evidence to the contrary, do not have the …. (shrink)

IntroductionAt present, in the UK, live lobe donation of the lung is generally considered in the context of patients with cystic fibrosis which is a life-threatening, inherited disease.1 However, if this technique is successfully developed it may be applicable to other patients with end stage lung disease. Cystic fibrosis is a disease where the major morbidity and mortality is due to pulmonary infection and respiratory failure.2 In l938 70% of patients born with CF died within one year (...) of birth, but now the average survival has improved to 32 years.1 The improved survival has been due to improved medical care, but also, and in very large measure, to the devotion of the families who have carried out time-consuming daily treatments such as chest physiotherapy, nebuliser treatment, high calorie diets etc. To these patients and their families lung transplantation brought new hope.3 The first successful transplant for CF was performed in the UK in 1985 and we now have patients alive and well more than ten years after transplantation. However, sadly, nearly 50% of patients with CF die on the transplant waiting list because of a shortage of donor organs from brain stem dead donors. This is a tragedy for the individual patient, the families and those who care for them. Is there a way forward?Can the number of organs available for transplantation be increased?Education of the public so that a relative of a brain dead individual will give permission for the organs to be used has been carried out for many years but only with a small increase in the number of available organs. “Required request” where doctors would be required, by law, to ask relatives of brain dead patients to consider transplantation and “assume consent” where consent to donation is assumed unless there is evidence to the contrary, do not have the …. (shrink)

Modern medicine emphasizes treatment of the sick. It is often said that the widespread genetic testing soon to follow the completion of the Human Genome Project will usher in a new era of preventive medicine. Such changes require new ways of thinking, however. For example, there may be nothing clinically wrong with a healthy patient who requests genetic testing, even if the tests reveal disease genes. Since all individuals have genetic skeletons in their closets, it is important to be careful (...) not to confuse having disease genes with having the diseases that they cause. Unfortunately, many in the public have adopted a kind of genetic determinism that sees genes as destiny: for example, having the gene associated with colon cancer means they will develop colon cancer. Physicians tend to be more careful, yet even they are not immune to subtle versions of genetic determinism. One example of this is the uncritical categorization of certain diseases as “genetic”. In fact, an adequate concept of genetic disease is extremely difficult to come by. The simplest notion would require a 1:1 correspondence between a disease and its genes, but this is the exception rather than the rule. For example, cystic fibrosis (CF) is often put forward as a good example of a genetic disease, since it seems to result from mutations in a single gene, CFTR. Even in this case, however, the exact relationship between CFTR mutations and disease is not clear, as virtually every possible combination of sweat chloride test results, genetic test results, and symptoms has been observed.[1] If a patient presents with the classic symptoms of CF and is found to have a mutation in the CFTR gene, the physician might understandably infer that the mutation caused the disease. But if an asymptomatic patient is tested and it is discovered that he or she has a CFTR mutation, it is unclear what this means. The doctor might tell the patient the gene is abnormal and that he or she is likely to develop pulmonary problems, etc., but it’s not really known whether even this qualified prognosis is true.. (shrink)

A recent study by Castellani et al. (JAMA 302(23):2573–2579, 2009) describes the population-level effects of the choices of individuals who underwent molecular carrier screening for cystic fibrosis (CF) in Veneto, in the northeastern part of Italy, between 1993 and 2007. We discuss some of the ethical issues raised by the policies and individual choices that are the subject of this study. In particular, (1) we discuss the ethical issues raised by the acquisition of genetic information through antenatal carrier testing; (...) (2) we consider whether by choosing to procreate naturally these couples can harm the resulting child and/or other members of society, and what the moral implications of such harm would be; (3) we consider whether by choosing to avoid natural procreation carrier couples can harm current or future individuals affected by cystic fibrosis; (4) we discuss whether programs that make carrier testing available can be considered eugenic programs. (shrink)

Poorly understood, linked in complex ways to ideas about race and European identity, and the focus today of an ethically vexed and rapidly expanding testing industry, cystic fibrosis is a relatively common life-threatening genetic disorder in the United States, the United Kingdom, and the European Union. Many genetic diseases are invisible to the general public, but CF is a high-profile genetic disease, often characterized as a “white” disease though it occurs in many populations. Over the last five years it (...) has become the focus of genetic screening programs of many kinds, but especially for newborns, all over the world. CF is also a scientifically interesting genetic disease. By the simple if imperfect .. (shrink)

Objective: Pulmonary complications could badly affect the recovery of neurological function and neurological prognosis of neurological critically ill patients. This study evaluated the effect of high-flow nasal cannula therapy on decreasing pulmonary complications in neurologically critically ill patients.Patients and Methods: The patients admitted to the intensive care unit with serious neurological disease and receiving oxygen therapy were retrospectively reviewed. Patients were divided into the HFNC group and the conventional oxygen therapy group. We analyzed the data within these two (...) groups, including patients’ baseline data, short-term outcomes of respiratory complications, general outcomes including hospital stay, ICU stay and mortality, and neurological functions. To analyze the relevant factors, we performed multivariable logistic regression analysis.Results: A total of 283 patients met the criteria, including 164 cases in the HFNC group and 119 cases in the COT group. The HFNC group had remarkably less mechanical ventilation requirement with lower phlegm viscosity. Even more, ICU stay and total hospital stay were significantly shortened in the HNFC group.Conclusion: HFNC decreased pulmonary complications in neurologically critically ill patients and improved recovery of neurological function and neurological prognosis. (shrink)

Pulmonary rehabilitation has demonstrated patients’ physiological and psychosocial improvements, symptoms reduction and health-economic benefits whilst enhances the ability of the whole family to adjust to illness. However, PR remains highly inaccessible due to lack of awareness of its benefits, poor referral and availability mostly in hospitals. Novel models of PR delivery are needed to enhance its implementation while maintaining cost-efficiency. We aim to implement an innovative community-based PR programme and assess its cost-benefit. A 12-week community-based PR will be implemented (...) in primary healthcare centres where programmes are not available. Healthcare professionals will be trained. 73 patients with CRD and their caregivers will compose the experimental group. The control group will include dyads age- and disease-matched willing to collaborate in data collection but not in PR. Patients/family-centred outcomes will be dyspnoea, fatigue, cough and sputum, impact of the disease, emotional state, number of exacerbations, healthcare utilisation, health-related quality of life and family adaptability/cohesion. Other clinical outcomes will be peripheral and respiratory muscle strength, muscle thickness and cross sectional area, exercise capacity, balance and physical activity. Data will be collected at baseline, at 12 weeks, at 3- and 6-months post-PR. Changes in the outcome measures will be compared between groups, after multivariate adjustment for possible confounders, and effect sizes will be calculated. A cost-benefit analysis will be conducted. This study will enhance patients access to PR, by training healthcare professionals in the local primary healthcare centres to conduct such programmes and actively involving caregivers. The cost-benefit analysis of this intervention will provide an evidence-based insight into the economic benefit of community-based PR in chronic respiratory diseases. The trial was registered in the ClinicalTrials. gov U.S. National Library of Medicine, on 10th January, 2019. (shrink)

BackgroundCommonly applied measures of symptoms of anxiety are not sensitive to disease-specific anxiety in patients with chronic obstructive pulmonary disease. There is a need for validated instruments measuring COPD-specific anxiety. Therefore, we translated the COPD-Anxiety Questionnaire into Danish and performed an initial validation of the psychometric properties in a sample of patients with COPD.Materials and MethodsTranslation procedures followed the World Health Organization guidelines. Participants with COPD completed questionnaires measuring COPD-specific anxiety, general psychological distress as well as variables related to (...) COPD, quality of life, and socio-demography.ResultsA total of 260 patients with COPD completed questionnaires. The Danish version of CAF-R-DK demonstrated acceptable Cronbach’s α values that were comparable with those of the original CAF. As expected, the CAF-R-DK showed positive correlations with convergent constructs and negative correlations with discriminant constructs. However, the results for specific subdomains of the CAF-R-DK indicated inconsistency in the underlying concept of disease-specific anxiety, which was also suggested based on the subsequent confirmatory and exploratory factor analyzes.ConclusionThe CAF could serve as an important supplement to generic psychological distress screening of patients with COPD in somatic health care settings, and the questionnaire is now available in Danish. Translation into other languages is needed with the purpose of obtaining data for further testing the psychometric properties of the questionnaire. (shrink)

Patients with chronic obstructive pulmonary disease are characterized by attenuated pulmonary function and are frequently reported with cognitive impairments, especially memory impairments. The mechanism underlying the memory impairments still remains unclear. We applied resting-state functional magnetic resonance imaging to compare the brain local activities with static and dynamic amplitude of low-frequency fluctuations among patients with COPD and healthy controls. Compared with HC, COPD patients exhibited decreased sALFF in the right basal ganglia and increased dALFF in the bilateral parahippocampal/hippocampal (...) gyrus. The reduced the left basal ganglia was associated with lower oxygen partial pressure. Besides, the increased dALFF in the left hippocampal/parahippocampal cortex was associated with poor semantic-memory performance and the increased dALFF in the left hippocampal/parahippocampal cortex was associated the forced vital capacity. The present study revealed the abnormal static and dynamic local-neural activities in the basal ganglia and parahippocampal/hippocampal cortex in COPD patient and its relationship with poor lung function and semantic-memory impairments. (shrink)

It may be unethical to deny children with cystic fibrosis access to ethically approved clinical trials from which they might benefitDespite advances in nutritional management, aggressive antibiotic usage, and physiotherapy, cystic fibrosis remains a life limiting illness with high morbidity that imposes considerable burdens on children and families.1 Although survival to 40 years is predicted for children born in 1990s, the median age of death in 2003 was 24.2 years .The pathophysiological features of CF are produced by a (...) defective gene on chromosome 7, resulting in the defective production of a protein that regulates cellular ion transport. Defective ion transport is thought to lead to increased mucus viscosity , with poor airway clearance, recurrent bacterial infection, lung damage, and death.Gene therapy , the insertion of a normally functioning gene into deficient host cells using a suitable vector, is a potential treatment or cure for diseases produced by single gene defects—for example, CF. Gene therapy does, however, have potential or actual risks, leading many to suggest that evidence of efficacy in adults should be demonstrated before trials are conducted in children. Many serious diseases in adults such as CF have their onset in childhood. If early treatment provides greater hopes of benefit, children may be more appropriate targets for GT in CF than adults. It may be unethical to deny them access to properly constructed, ethically approved clinical trials from which they might benefit.Since research in children should be scientifically valid, in the child’s best interests, and the subject of valid consent, this article will consider these parameters in relation to trials of GT in children with CF. Because of the importance of consumer participation in the design of research we present the results of a questionnaire about GT trials delivered …. (shrink)

The advent of prenatal genetic diagnosis has sparked debates among ethicists and philosophers regarding parental responsibility towards potential offspring. Some have attempted to place moral obligations on parents to not bring about children with certain diseases in order to prevent harm to such children. There has been no rigorous evaluation of cystic fibrosis in this context. This paper will demonstrate cystic fibrosis to have unique properties that make it difficult to categorise among other diseases with the goal of (...) promulgating a reproductive rule. Once this is established, it will be demonstrated that procreative rules that appeal to future health are inadequate in the era of advancing genetic knowledge. Utilising a specification of Joel Feinberg's ‘open future’ concept outlined by Matteo Mameli, it will offer an analysis of parental obligation that does not constrain parents of potential children with cystic fibrosis with a moral obligation not to bring them about. (shrink)

There are two competing accounts for a theory for human action proposed by Catholic theologians working within the received moral tradition today: a hylomorphic account and an intentional account. In this article, the author compares each of the rival theories for its ability to explain both the structure and morality of the human acts surrounding the elective termina­tion of the pregnancy of a woman with pulmonary arterial hypertension. This scenario of PAH is a superb test case to compare the (...) explanatory power of the two rival action theories. The author’s analysis reveals that the hylomorphic account is the superior account, which can explain better not only the norma­tive conclusions of the Catholic moral tradition but also our lived experience as acting persons in a world governed by cause-and-effect relationships. National Catholic Bioethics Quarterly 11.3 (Autumn 2011): 503–518. (shrink)

Abstractabstract:Long before COVID-19 made social distancing familiar, people with cystic fibrosis (CF) already practiced such behaviors. CF is held up as a classic example of genetic disease, yet people with CF are also susceptible to bacteria from the environment and from other CF patients. Starting in the 1980s, a bacterial epidemic in the CF population highlighted clashing priorities of connection, physical safety, and environmental protection. Policymakers ultimately called for the physical separation of people with CF from one another via (...) recommendations that reconfigured the CF community. Simultaneously, medical researchers recognized that one highly transmissible CF pathogen called cepacia was being developed for environmental applications and got the EPA to limit cepacia's environmental deployment. Environmental regulations speak to the challenge of useful microbes that harm a minority, but CF cross-infection also involves legal implications for microbial and genetic discrimination, social consequences for CF communities, and ethical questions about balancing autonomy, harms, and benefits. As scientists increasingly study connections between host genetics, microbial genetics, and infectious risks, CF is a vital referent. (shrink)

There are two competing accounts for a theory for human action proposed by Catholic theologians working within the received moral tradition today: a hylomorphic account and an intentional account. In this article, the author compares each of the rival theories for its ability to explain both the structure and morality of the human acts surrounding the elective termina­tion of the pregnancy of a woman with pulmonary arterial hypertension. This scenario of PAH is a superb test case to compare the (...) explanatory power of the two rival action theories. The author’s analysis reveals that the hylomorphic account is the superior account, which can explain better not only the norma­tive conclusions of the Catholic moral tradition but also our lived experience as acting persons in a world governed by cause-and-effect relationships. National Catholic Bioethics Quarterly 11.3 : 503–518. (shrink)

HLDING A‐G and HEGGDAL K. Nursing Inquiry 2012; 19: 345–356 Patients’ experiences of health transitions in pulmonary rehabilitationPeople who live with chronic obstructive pulmonary disease (COPD) experience major changes in health. Coping with the illness and caring for themselves places extensive demands on them. Thus, pulmonary rehabilitation (PR) is recommended as a means to facilitate healthy transitions in everyday life with COPD. This study explores the experience of patients with COPD in terms of their transitions in health (...) during and after PR. The research was inspired by interpretive phenomenology. Thirty‐three individual qualitative interviews were conducted with eighteen patients recruited from Norwegian PR units. A thematic analysis of the interviews was performed. The interviewees described participation in PR as a time of increasing awareness of opportunities for health and well‐being with strengthened hope. The year following PR was dominated by their ongoing challenge to acknowledge limitations and explore opportunities in everyday life. Continuation of healthy transitions was facilitated by peer and professional support. The study highlights the personal resources that patients with COPD have access to in order to promote their own health. The study also highlights their vulnerability during illness and rehabilitation. The findings critique time‐limited PR and support the current trends towards patient‐centred rehabilitation efforts that incorporate user involvement and self‐management education. (shrink)

Background: Decisions regarding whether or not to institute mechanical ventilation during the later stages of chronic obstructive pulmonary disease is challenging both ethically, emotionally and medically. Caring for these patients is a multifaceted process where nurses play a crucial role. Research question and design: We have investigated how nurses experienced their own role in decision-making processes regarding mechanical ventilation in later stages of chronic obstructive pulmonary disease and how they consider the patients’ role in these processes. We applied (...) a qualitative approach, with six focus-group interviews of nurses (n = 26). Ethical considerations: The Regional Committees for Medical and Health Research Ethics approved the study. Voluntary informed consent was obtained. Findings: The nurses found themselves operating within a cure-directed treatment culture wherein they were unable to stand up for the caring values. They perceived their roles and responsibilities in decision-making processes regarding mechanical ventilation to patients as unclear and unsatisfactory. They also experienced inadequate interdisciplinary cooperation. Discussion: Lack of communication skills, the traditional hierarchical hospital culture together with operating in a medical-orientated treatment culture where caring values is rated as less important might explain the nurses’ absence in participation in the decision about mechanical ventilation. Conclusion: To be able to advocate for the patients’ and their own right to be included in decision-making processes, nurses need an awareness of their own responsibilities. This requires personal courage, leadership who are capable of organising common interpersonal meetings and willingness on the part of the physicians to include and value the nurses’ participation in decision-making processes. (shrink)

The practice of communicating research findings to participants has been identified as important in the research ethics literature, but little research has examined empirically how this occurs and...

The Mycobacterium Tuberculosis complex is a group of species of Mycobacteria involved in a serious bacterial disease which infects the respiratory system and organs. Multi-drug resistant (MDR) strains have been produced as a result of the fast emergence of resistance against first-line anti-tuberculosis medicines in recent years worldwide. The objective of this study is to determine alternatives to anti-mycobacterial antibiotics, such as Manuka honey and Indian costus. MTB isolates (???? = 15) were evaluated for their susceptibility to Manuka honey graded (...) as +15 and Indian costus by using different concentrations. Among the TB isolates (???? = 15) tested, four (27%) isolates were resistant at 15% v/v honey, while, at 18% v/v of Manuka honey, two (13%) isolates were found to be resistant. Resistance was not seen at honey concentrations of 20% v/v. On the other hand, Indian costus had a slight effectiveness at concentrations of 20% and 25%, affecting only two and five isolates of Mycobacteria, respectively; however, all isolates were inhibited at a concentration of 33% v/v of Indian costus. The present study clearly demonstrates that supposed alternatives (Manuka honey graded as +15 and Indian costus) possess significant anti-mycobacterial activity in vitro; however, further clinical trials should be performed to corroborate our initial findings. (shrink)

Technological advances force redefinition of action-mandating concepts and language through complex social, political and economic tendencies that collectively determine what has been dubbed “the technological imperative.” The reverse is also true: redefinition of concepts shapes and guides the direction of technological development through shaping public beliefs and expectations. A powerful and far-reaching example of such occurred with the redefinition of “death” and the concept’s transformed relationship to transplantation technology.