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BACKGROUND: Manual and mechanical cough-augmentation techniques can improve peak cough flow (PCF) in patients with respiratory insufficiency caused by neuromuscular disease. METHODS: We studied cough-augmentation techniques in 179 clinically stable patients with various neuromuscular diseases. We measured vital capacity (VC), maximum expiratory pressure (MEP), and PCF, with and without 3 cough-augmentation techniques: manually assisted cough (MAC); breath-stacking (in a subgroup of 60 patients receiving noninvasive mechanical ventilation); and breath-stacking in combination with MAC (also in the 60-patient subgroup). We analyzed the data with the receiver operating characteristic (ROC), to predict the lower limits (assisted PCF >/= 180 L/min) and upper limits (assisted PCF < unassisted PCF) of effectiveness of the 3 cough-augmentation techniques. RESULTS: The lower limit of effective assisted cough with MAC, breath-stacking, and breath-stacking plus MAC was best predicted by VC > 1,030 mL (ROC 0.86, P < .001), VC > 558 mL (ROC 0.92, P < .001), and VC > 340 mL (ROC 0.90, P < .001). The upper limit of effective MAC was best predicted by MEP > 34 cm H(2)O (ROC 0.89, P < .001), whereas the ROC prediction of the upper limit of effective cough with breath-stacking and with breath-stacking plus MAC was not better than random. With each of the cough-augmentation techniques the benefits decreased linearly with increasing MEP and VC (P < .001). Compared to MAC and breath-stacking alone, breath-stacking plus MAC best improved unassisted PCF (P < .001). CONCLUSIONS: In clinically stable patients with neuromuscular diseases, the effectiveness of cough-augmentation techniques can be predicted with measurements of maximum respiratory capacity. Patients with VC > 340 mL and MEP < 34 cm H(2)O would optimally benefit from the combination of breath-stacking plus manually assisted cough to improve PCF to > 180 L/min. [ABSTRACT FROM AUTHOR]

Background and Purpose: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment., Materials and Methods: Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade ≥ 3 in IMPT vs IMRT treated patients., Results: 271 patients were enrolled (IMPT: n = 71, IMRT: n = 200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58 % were male, 36 % had squamous NSCLC. The incidence of lymphopenia grade ≥ 3 during CCRT was 67 % and 47 % in the IMRT and IMPT group, respectively (OR 2.2, 95 % CI: 1.0-4.9, P = 0.03). The incidence of anemia grade ≥ 3 during CCRT was 26 % and 9 % in the IMRT and IMPT group respectively (OR = 4.9, 95 % CI: 1.9-12.6, P = 0.001). IMPT was associated with a lower rate of Performance Status (PS) ≥ 2 at day 21 and 42 after CCRT (13 % vs. 26 %, P = 0.04, and 24 % vs. 39 %, P = 0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74 % vs. 52 %, OR 0.35, 95 % CI: 0.16-0.79, P = 0.01)., Conclusion: IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Adjuvant durvalumab is the standard of care for patients with stage III unresectable non-small cell lung cancer (NSCLC), without progression after concurrent chemo-radiation (CCRT). Patients with stage III NSCLC harbouring epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangements do not seem to benefit from durvalumab. Data are lacking about patients harbouring other driver genomic alterations (dGA). We performed a multicentre (N = 4, Netherlands and Italy) retrospective study including consecutive patients with unresectable stage III NSCLC and treated with CCRT-with or without adjuvant durvalumab-between 2016 and 2022. We enrolled 271 patients; 130 of which received adjuvant durvalumab. Sixty-six patients had dGA (41 KRAS mutations, 4 EGFR common mutations and 21 uncommon dGA). In the entire population, the median PFS was 24.9 months (95% CI 17.5-32.4) and 12.6 months (95% CI 9.0-16.1) with and without durvalumab (p = 0.001). In the dGA group (excluding common EGFR), mPFS was 12.3 months (95% CI 7.8-16.8) with and 7.6 (95% CI 3.4-11.9) without durvalumab (p = 0.038). For patients with KRAS mutations, mPFS was 12.3 months (95% CI 3.6-20.9) with and 7.2 months (95% CI 1.8-12.6) without durvalumab (p = 0.12). Among patients with uncommon dGA, mPFS was 12.9 months (95% CI 8.4-17.4) with and 7.6 months (95% CI 1.4-14) without durvalumab (p = 0.23). We have shown a meaningful survival benefit of adjuvant durvalumab in patients harbouring KRAS mutations and uncommon dGA. This is the largest stage III NSCLC cohort showing the efficacy of durvalumab in patients with uncommon dGA. Further prospective studies are needed to confirm our results., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FC: Lilly, Travel expenses, Institutional; AstraZeneca, Local PI, Institutional. DDR: AstraZeneca, Research Grant, Institutional; AstraZeneca, Steering Committee Member, Institutional, AstraZeneca, Coordinating PI, Institutional, BeiGene, Funding, Institutional, BMS, Research Grant, Institutional, BMS, Coordinating PI, Institutional, Olink, Funding, No financial interest. Philips Health, Steering Committee Member, Institutional, Varian, Research Grant, Institutional. MS: No conflict of interest to declare. RW: No conflict of interest to declare. AvdW: Received research grants from AstraZeneca, Boehringer-Ingelheim, Pfizer, Roche and Takeda outside the current work. Was involved in advisory boards of AstraZeneca, Janssen, Lilly, Roche and Takeda and was speaker in educational meetings sponsored by AstraZeneca, BMS, Lilly, Pfizer and Roche. Involved in clinical studies for AstraZeneca, Amgen, Blueprint medicine, Nuvalent, Novartis, Merck, Pfizer, Roche and Takeda. Payments from Dutch Guidelines for NSCLC. All finances received by the UMCG. Non-financial: Board Member Dutch Oncology Group (NVALT), Member of Patient Panel of Longkanker Nederland and Member of Patient Advisory Panel of ROS1ders. MA: No conflict of interest to declare. LH: Amgen, Advisory Board, Institutional; AstraZeneca, Other, Personal, Mentorship with key opinion leaders funded by AstraZeneca; AstraZeneca, Invited Speaker, Institutional for educational webinar; Bayer, Invited Speaker, Institutional; Educational webinar/interview, Benecke, Invited Speaker, Personal, payment for post ASCO/ESMO/WCLC presentations, educational committee member; BMS, Advisory Board, Institutional; Boehringer Ingelheim, Advisory Board, Institutional; high5oncology, Invited Speaker, Institutional, payment for post ESMO/ASCO discussion; Janssen, Advisory Board, Institutional; Janssen, Other, Institutional, Educational webinar. Lilly, Advisory Board, Institutional; Lilly, Invited Speaker, Institutional, for educational webinar; Medtalks, Invited Speaker, Personal, for webinars; Merck, Advisory Board, Institutional; MSD, Advisory Board, Institutional; MSD, Invited Speaker, Institutional, educationals; Novartis, Advisory Board, Institutional; Pfizer, Advisory Board, Institutional; Roche, Other, Personal, travel support; Roche, Other, Institutional, performing interviews at conference; Roche, Advisory Board, Institutional, one time also personal; Takeda, Advisory Board, Institutional. Takeda, Other, Institutional, podcast on brain metastases; VJOncology, Invited Speaker, Personal, payment for post ASCO round table discussion; Dutch guidelines NSCLC, brain metastases and leptomeningeal metastases, Other, Personal, member of the committee that revised these guidelines; Abbvie, Local PI, Institutional; AstraZeneca, Local PI, Institutional; AstraZeneca, Research Grant, Institutional; Blueprint Medicines, Local PI, Institutional; Boehringer Ingelheim, Research Grant, Institutional; Gilead, Local PI, Institutional; GSK, Local PI, Institutional; Merck, Research Grant, Institutional, donation for health care improvement project; Merck Serono, Local PI, Institutional; Mirati, Local PI, Institutional, MSD, Local PI, Institutional; Novartis, Local PI, Institutional; Pfizer, Research Grant, Institutional, funding for healthcare improvement project; Roche, Local PI, Institutional; Roche, Research Grant, Institutional; Takeda, Local PI, Institutional, Research Grant, Institutional. Non-financial interests: EORTC, chair metastatic NSCLC for lung cancer group, NVALT, secretary NVALT studies foundation., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Air stacking improves cough effectiveness in people with Duchenne muscular dystrophy (DMD) and respiratory muscle weakness. However, it is not known whether air stacking is more effective via a resuscitator bag or a home ventilator., Methods: This prospective randomized study investigated the effect of air stacking via a volume-cycled home ventilator versus via a resuscitator bag in participants with DMD. Maximum insufflation capacity and peak expiratory flow during spontaneous (cough peak flow) and air stacking-assisted cough maneuvers (air stacking-assisted cough peak flow) were measured., Results: Fifty-two adult DMD subjects receiving noninvasive ventilation were included in the study: 27 participants performed air stacking via their home ventilator (home-ventilator group; age = 25.3 ± 5.1 y; forced vital capacity (FVC) = 809 ± 555 mL), and 25 participants used a resuscitator bag (resuscitator-bag group; age = 24.7 ± 5.7 y, FVC = 807 ± 495 mL). Following a single training session, air stacking could be performed successfully by 89% (home ventilator) and 88% (resuscitator bag) of participants. There were comparable maximum insufflation capacities (1,481 mL for the home-ventilator group vs 1,344 mL for the resuscitator-bag group, P = .33) and mean air stacking-assisted cough peak flow values (199 L/min for the home-ventilator group vs 186 L/min for the resuscitator-bag group, P = .33) between techniques. Air stacking-assisted cough peak flow increased significantly compared with baseline in both groups (mean increase: +51% [home ventilator] vs +49% [resuscitator bag], P < .001), with individual air stacking-assisted cough peak flow improvements ranging from -20 to 245%., Conclusions: Cough augmentation is an important component of the respiratory management of people with a neuromuscular disorder. No difference in cough effectiveness as measured by air stacking-assisted cough peak flow was found in air stacking via a ventilator compared with via a resuscitator bag. Both methods achieved mean air stacking-assisted cough peak flow values of >160 L/min. Provision of an inexpensive resuscitator bag can effectively improve cough capacity, and it is simple to use, which may improve access to respiratory care in people with DMD., (Copyright © 2016 by Daedalus Enterprises.)

Background: In patients with Duchenne muscular dystrophy (DMD), implementation of mechanical ventilation depends on sleep investigation and measurement of CO2 tension. The objective of this cross-sectional study was to determine which noninvasive lung function parameter best predicts nocturnal hypercapnia and diurnal hypercapnia in these patients., Methods: According to transcutaneous CO2 (TcCO2) measurement, 114 DMD patients were classified into three groups: nocturnal hypercapnia (n = 38) [group N], diurnal hypercapnia (n = 39), despite nocturnal ventilation (group D), and 24-h normocapnia and spontaneous breathing (n = 37) [group S] as control. TcCO2 tension and lung function variables included vital capacity (VC) and maximal inspiratory pressure (MIP), and breathing pattern variables included tidal volume (Vt) and respiratory rate (RR), measured at the time of group inclusion. The rapid and shallow breathing index (RSBI [RR/Vt]) and Vt/VC ratio were calculated. Areas under the curve from the receiver operating characteristic (ROC) were calculated for those parameters., Results: Compared to group S, lung function was significantly worse in group N and group D. VC, RR, and RSBI distinguished group S from group N by ROC comparison. Cut-off values of VC < or = 680 mL (ROC, 0.968), MIP < or = 22 cm H2O (ROC, 0.928), and Vt/VC > 0.33 (ROC, 0.923) accurately discriminated group D from group N, but RSBI, RR, and Vt did not., Conclusions: Lung function is useful to predict nocturnal hypercapnia in patients with DMD. Moreover, VC < 680 mL is very sensitive to predict daytime hypercapnia.

Introduction: Home mechanical ventilation is used to treat chronic alveolar hypoventilation. Maintenance protocols for home ventilation circuits (HVC) remain empirical and unproven. We have investigated (1) the cleanliness and sterility of the HVC used by home ventilated patients and (2) the efficiency of tubing cleaning and decontamination protocols recommended to them and used for 12 months or more., Method: HVC cleanliness was assessed in 39 severe restrictive ventilated patients (16 (T) tracheostomy vs. 23 (N) noninvasive) and in 7 new valves as control. In the first experiment (Exp1), a visual and bacteriologic inspection of the expiratory valve (Eva) was conducted during a consultation in our centre. Eva visual cleanliness was assessed on a 10-point scale and Eva bacteriologic contamination analysis was performed on a dry smear. In the second experiment (Exp2), these analyses were repeated after a cleaning sequence chosen at random, either chemical (ammonium-chlorhexidine complex) (A) or mechanical by dishwasher (B)., Results: In Exp1, 69% of Eva were dirty. Dirtiness was worse in (T) than in (N) (5.3 vs. 2; p<0.001). There was a significant positive correlation between visual cleanliness and bacteriologic contamination (r=0.56; p<0.001). Eva in group (T) were more contaminated than in group (N) (p<0.001). Eva contamination rates reached 22% in group (N) but without the presence of any potentially pathogenic organisms (PPO) and 81% in group (T) where 19% were PPO. In Exp2, EVA visual cleanliness was better after dishwasher cleaning (B) compared to chemical (A) (0.16 vs. 1.05; p<0.001) with similar bacteriological decontamination., Conclusion: HVC from noninvasive ventilated patients are dirty but not contaminated by PPO. We recommend washing them in a dishwasher or with detergent and hot water without specific disinfection. PPO contaminated 1/5 of invasive HVC, for which we recommend dishwasher cleaning. Decontamination is only indicated when tubing is visually very dirty or/and when tracheostomized patients are particularly sensitive to respiratory tract infections. The expiratory valve must be carefully washed specifically, with care that its balloon is not placed under water.

Objective: To determine the effects of intrapulmonary percussive ventilation (IPV) on mucus clearance in tracheostomized Duchenne muscular dystrophy patients., Methods: We studied 8 patients, 5 of whom had mucus hypersecretion (> 30 mL/d). In a randomized, cross-over study we compared assisted mucus clearance techniques with and without IPV. There were 2 treatment sequences and each patient received 5 consecutive days of each treatment sequence, delivered 3 times a day. One sequence consisted of (1) assisted mucus clearance technique (AMCT, which involves forced expiratory technique and manual assisted cough), (2) endotracheal suctioning, (3) nebulizer administration of 5 mL of 0.9% sodium chloride solution for 5 min, (4) a second AMCT session, (5) endotracheal suctioning, (6) 45 min after the end of the nebulizer treatment a third AMCT session, (7) endotracheal suctioning. The other treatment sequence was the same except that it included IPV during the 5-min nebulizer treatment. The collected secretions were weighed. Vital capacity was measured once, before the treatments. Heart rate, respiratory rate, oxyhemoglobin saturation, end-tidal carbon dioxide, airway resistance, and peak expiratory flow were measured before and at 45 min after the treatments. Mean values were compared using analysis of variance with repeated measures., Results: In patients with hypersecretion the mean +/- SD weight of the collected secretions was significantly higher with IPV (6.53 +/- 4.77 g vs 4.57 +/- 3.50 g, p = 0.01). Heart rate, respiratory rate, oxyhemoglobin saturation, end-tidal carbon dioxide, airway resistance, and peak expiratory flow did not differ statistically between the 2 treatments., Conclusions: IPV is a safe airway clearance method for tracheostomized Duchenne muscular dystrophy patients, and this preliminary study suggests that IPV increases the effectiveness of assisted mucus clearance techniques.

Human recombinant myeloperoxidase was evaluated in a cell-free system for its inactivation properties on the replication of human immunodeficiency virus, HTLV-IIIB. In the presence of a hydrogen peroxide generating system (glucose and glucose oxidase) and sodium thiocyanate, the recombinant enzyme inhibited virus-induced syncytium formation and viral replication without causing any cytopathic effects on SupT1 reporter cells. In addition, U937 monocytoid cells, chronically infected with HIV1, were exposed to recombinant myeloperoxidase (10 U/ml) and monitored during 48 h for the accumulation of intracellular p24 viral antigen. Under these conditions, the recombinant enzyme significantly reduced intracellular viral replication without affecting cell viability.

The sensitivity of blood culture isolates to the bactericidal activity of normal human serum (NHS) has been studied in 101 patients with gram-negative sepsis. These results were compared with clinical status and outcome, and to the presence of specific IgG or IgM antibodies to O antigens of bacteraemic strains in autologous serum. 23% of the strains were markedly resistant, 27% markedly sensitive and 50% intermediately sensitive to the bactericidal activity of NHS. Shock or death occurred more frequently in immunocompromised patients and those infected with serum-resistant strains. IgG antibody titres to O antigens were significantly lower in patients with serum-resistant organisms regardless of their immune status. Resistance to natural bactericidal antibodies and low immunogenicity of the infecting organism, plus immunodeficiency in the host, may account for apparent increased virulence of some gram-negative bacilli.