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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDisplayedQuote" id="dsq0005"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#8220;<span class="elsevierStyleItalic">I speak not to disprove what Brutus spoke&#44; But here I am to speak what I do know</span>&#8221; &#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span></p><p id="par0010" class="elsevierStylePara elsevierViewall">We thank Grogono et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> for their interest in our review on management of dyspnoea in patients with <span class="elsevierStyleBold">advanced</span> respiratory diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">3</span></a> Breathlessness requires much more attention by clinicians and researchers&#44; as a major health problem around the world for millions of people<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">4</span></a> and their letter may contribute to the discussion&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Inhaled furosemide</span>&#46; Grogono et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> give more details of their study in normal volunteers <a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">5</span></a> as well as of other studies&#46; We fully agree with their conclusion that &#8220;<span class="elsevierStyleBold"><span class="elsevierStyleItalic">More</span></span><span class="elsevierStyleItalic">research with inhaled furosemide is justified</span>&#8221;&#46; That&#8217;s why in our review we concluded that &#8220;<span class="elsevierStyleItalic">based on available data&#44; its &#40;nebulised furosemide&#8230;&#41; use for the routine management of dyspnoea in</span><span class="elsevierStyleBold"><span class="elsevierStyleItalic">terminal</span></span><span class="elsevierStyleItalic">patients is still either controversial or not indicated</span>&#46;&#8221; Indeed we are unaware of any guideline recommending the use of inhaled furosemide in patients with <span class="elsevierStyleBold">advanced</span> respiratory diseases&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Opioids</span>&#46; Practitioners and researchers have paid greater attention to management of pain than dyspnoea&#44; and patients with <span class="elsevierStyleBold">end- stage</span> respiratory diseases are less likely to undergo palliative care than patients with cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">6-8</span></a> The controversy on the use of opioids in respiratory diseases is long standing&#44; and we <span class="elsevierStyleItalic">don&#8217;t disprove what anyone spoke&#44; we just speak what we do know</span>&#46; Evidence based international guidelines recommend the use of opioids in <span class="elsevierStyleItalic">appropriate</span> doses&#44; <span class="elsevierStyleItalic">formulations and schedules of administration</span> in patients with <span class="elsevierStyleBold">advanced</span> chronic respiratory diseases&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">9&#44;10</span></a> but we understand authors&#8217; concern about potential long-term adverse effects&#44; lack of effectiveness or risk of addiction&#46; However&#44; we described evidence based management of patients with <span class="elsevierStyleBold">advanced</span> or <span class="elsevierStyleBold">end-stage</span> respiratory diseases with poor short-term prognosis and life expectancy which would be probably not long enough to develop such potential long-term side effects&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Nobody denies that respiratory depression is a predictable adverse effect from a significant opioid <span class="elsevierStyleItalic">overdose</span>&#44; while we need further clinical trials to better individualize treatment&#46; Grogono et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> blame us for ignoring the &#8220;<span class="elsevierStyleItalic">opioid crisis</span>&#8221; quoting a paper <a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">11</span></a> on &#8220;Opioid <span class="elsevierStyleItalic">Overdose&#8221;</span> induced by illegal use or pain killers and not including <span class="elsevierStyleItalic">even once</span> the words <span class="elsevierStyleItalic">&#8220;</span><span class="elsevierStyleBold"><span class="elsevierStyleItalic">dyspnea</span></span>&#8221; or &#34;breathlessness&#34;&#46; <span class="elsevierStyleItalic">Overdose</span> in medicine means malpractice and this is not the case of guidelines&#46; Illegal use or painkillers do not refer to the issue of our review&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">3</span></a> As a matter of fact our review<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">3</span></a> underlined the &#8220;<span class="elsevierStyleItalic">need to be aware of and treat adverse effects</span>&#8221; while suggesting a therapeutical escalation exploiting all available pharmacological and non pharmacological tools described in the review&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Finally nobody portrayed &#8220;<span class="elsevierStyleItalic">those who harbour legitimate concerns about opioid safety as human rights violators</span>&#8221;&#44; but we do think that avoiding <span class="elsevierStyleItalic">all</span> unpleasant and distressful symptoms&#44; not only pain&#44; in <span class="elsevierStyleBold">terminal</span> conditions <span class="elsevierStyleBold">IS</span> a human right&#46; Whoever has treated or even only seen an <span class="elsevierStyleBold">end-stage</span> dyspnoeic patient with pulmonary fibrosis asking for help&#44; knows what we are talking about&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion Grogono et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> criticize us for lack of <span class="elsevierStyleItalic">&#8220;full&#44; accurate and balanced critical appraisal of the evidence&#8221;</span> just because they disagree with some of our evidence based ideas &#40;or what they attribute to us&#41; but we could not agree more with their recommendation&#46; In our &#40;unfortunately&#8230;&#46;&#41; long life as researchers and clinicians we have always applied that principle&#44; as is the case of this review&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">3</span></a> however in all scientific controversies with our peers we have always tried to rebut &#40;rightly or wrongly&#41; only what they truly meant&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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Letter to the Editor
Strategies to relieve dyspnoea in patients with advanced chronic respiratory diseases. A narrative review. Authors’ reply
Nicolino Ambrosino
Corresponding author
nico.ambrosino@gmail.com

Corresponding author.
, Claudio Fracchia
Istituti Clinici Scientifici Maugeri, Istituto di Montescano, Italy
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDisplayedQuote" id="dsq0005"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#8220;<span class="elsevierStyleItalic">I speak not to disprove what Brutus spoke&#44; But here I am to speak what I do know</span>&#8221; &#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span></p><p id="par0010" class="elsevierStylePara elsevierViewall">We thank Grogono et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> for their interest in our review on management of dyspnoea in patients with <span class="elsevierStyleBold">advanced</span> respiratory diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">3</span></a> Breathlessness requires much more attention by clinicians and researchers&#44; as a major health problem around the world for millions of people<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">4</span></a> and their letter may contribute to the discussion&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Inhaled furosemide</span>&#46; Grogono et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> give more details of their study in normal volunteers <a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">5</span></a> as well as of other studies&#46; We fully agree with their conclusion that &#8220;<span class="elsevierStyleBold"><span class="elsevierStyleItalic">More</span></span><span class="elsevierStyleItalic">research with inhaled furosemide is justified</span>&#8221;&#46; That&#8217;s why in our review we concluded that &#8220;<span class="elsevierStyleItalic">based on available data&#44; its &#40;nebulised furosemide&#8230;&#41; use for the routine management of dyspnoea in</span><span class="elsevierStyleBold"><span class="elsevierStyleItalic">terminal</span></span><span class="elsevierStyleItalic">patients is still either controversial or not indicated</span>&#46;&#8221; Indeed we are unaware of any guideline recommending the use of inhaled furosemide in patients with <span class="elsevierStyleBold">advanced</span> respiratory diseases&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Opioids</span>&#46; Practitioners and researchers have paid greater attention to management of pain than dyspnoea&#44; and patients with <span class="elsevierStyleBold">end- stage</span> respiratory diseases are less likely to undergo palliative care than patients with cancer&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">6-8</span></a> The controversy on the use of opioids in respiratory diseases is long standing&#44; and we <span class="elsevierStyleItalic">don&#8217;t disprove what anyone spoke&#44; we just speak what we do know</span>&#46; Evidence based international guidelines recommend the use of opioids in <span class="elsevierStyleItalic">appropriate</span> doses&#44; <span class="elsevierStyleItalic">formulations and schedules of administration</span> in patients with <span class="elsevierStyleBold">advanced</span> chronic respiratory diseases&#44;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">9&#44;10</span></a> but we understand authors&#8217; concern about potential long-term adverse effects&#44; lack of effectiveness or risk of addiction&#46; However&#44; we described evidence based management of patients with <span class="elsevierStyleBold">advanced</span> or <span class="elsevierStyleBold">end-stage</span> respiratory diseases with poor short-term prognosis and life expectancy which would be probably not long enough to develop such potential long-term side effects&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Nobody denies that respiratory depression is a predictable adverse effect from a significant opioid <span class="elsevierStyleItalic">overdose</span>&#44; while we need further clinical trials to better individualize treatment&#46; Grogono et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> blame us for ignoring the &#8220;<span class="elsevierStyleItalic">opioid crisis</span>&#8221; quoting a paper <a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">11</span></a> on &#8220;Opioid <span class="elsevierStyleItalic">Overdose&#8221;</span> induced by illegal use or pain killers and not including <span class="elsevierStyleItalic">even once</span> the words <span class="elsevierStyleItalic">&#8220;</span><span class="elsevierStyleBold"><span class="elsevierStyleItalic">dyspnea</span></span>&#8221; or &#34;breathlessness&#34;&#46; <span class="elsevierStyleItalic">Overdose</span> in medicine means malpractice and this is not the case of guidelines&#46; Illegal use or painkillers do not refer to the issue of our review&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">3</span></a> As a matter of fact our review<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">3</span></a> underlined the &#8220;<span class="elsevierStyleItalic">need to be aware of and treat adverse effects</span>&#8221; while suggesting a therapeutical escalation exploiting all available pharmacological and non pharmacological tools described in the review&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Finally nobody portrayed &#8220;<span class="elsevierStyleItalic">those who harbour legitimate concerns about opioid safety as human rights violators</span>&#8221;&#44; but we do think that avoiding <span class="elsevierStyleItalic">all</span> unpleasant and distressful symptoms&#44; not only pain&#44; in <span class="elsevierStyleBold">terminal</span> conditions <span class="elsevierStyleBold">IS</span> a human right&#46; Whoever has treated or even only seen an <span class="elsevierStyleBold">end-stage</span> dyspnoeic patient with pulmonary fibrosis asking for help&#44; knows what we are talking about&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion Grogono et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">2</span></a> criticize us for lack of <span class="elsevierStyleItalic">&#8220;full&#44; accurate and balanced critical appraisal of the evidence&#8221;</span> just because they disagree with some of our evidence based ideas &#40;or what they attribute to us&#41; but we could not agree more with their recommendation&#46; In our &#40;unfortunately&#8230;&#46;&#41; long life as researchers and clinicians we have always applied that principle&#44; as is the case of this review&#44;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">3</span></a> however in all scientific controversies with our peers we have always tried to rebut &#40;rightly or wrongly&#41; only what they truly meant&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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Pulmonology

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