We thank Grogono et al.2 for their interest in our review on management of dyspnoea in patients with advanced respiratory diseases.3 Breathlessness requires much more attention by clinicians and researchers, as a major health problem around the world for millions of people4 and their letter may contribute to the discussion.

Inhaled furosemide. Grogono et al.2 give more details of their study in normal volunteers 5 as well as of other studies. We fully agree with their conclusion that “Moreresearch with inhaled furosemide is justified”. That’s why in our review we concluded that “based on available data, its (nebulised furosemide…) use for the routine management of dyspnoea interminalpatients is still either controversial or not indicated.” Indeed we are unaware of any guideline recommending the use of inhaled furosemide in patients with advanced respiratory diseases.

Opioids. Practitioners and researchers have paid greater attention to management of pain than dyspnoea, and patients with end- stage respiratory diseases are less likely to undergo palliative care than patients with cancer.6-8 The controversy on the use of opioids in respiratory diseases is long standing, and we don’t disprove what anyone spoke, we just speak what we do know. Evidence based international guidelines recommend the use of opioids in appropriate doses, formulations and schedules of administration in patients with advanced chronic respiratory diseases,9,10 but we understand authors’ concern about potential long-term adverse effects, lack of effectiveness or risk of addiction. However, we described evidence based management of patients with advanced or end-stage 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.

Nobody denies that respiratory depression is a predictable adverse effect from a significant opioid overdose, while we need further clinical trials to better individualize treatment. Grogono et al.2 blame us for ignoring the “opioid crisis” quoting a paper 11 on “Opioid Overdose” induced by illegal use or pain killers and not including even once the words “dyspnea” or "breathlessness". Overdose in medicine means malpractice and this is not the case of guidelines. Illegal use or painkillers do not refer to the issue of our review,3 As a matter of fact our review3 underlined the “need to be aware of and treat adverse effects” while suggesting a therapeutical escalation exploiting all available pharmacological and non pharmacological tools described in the review.

Finally nobody portrayed “those who harbour legitimate concerns about opioid safety as human rights violators”, but we do think that avoiding all unpleasant and distressful symptoms, not only pain, in terminal conditions IS a human right. Whoever has treated or even only seen an end-stage dyspnoeic patient with pulmonary fibrosis asking for help, knows what we are talking about.

In conclusion Grogono et al.2 criticize us for lack of “full, accurate and balanced critical appraisal of the evidence” just because they disagree with some of our evidence based ideas (or what they attribute to us) but we could not agree more with their recommendation. In our (unfortunately….) long life as researchers and clinicians we have always applied that principle, as is the case of this review,3 however in all scientific controversies with our peers we have always tried to rebut (rightly or wrongly) only what they truly meant.