Thoughtful prescription of inhaled medication has the potential to reduce inhaler-related greenhouse gas emissions by 85.

INTRODUCTION: Both physicians and patients are increasingly aware of the environmental impacts of medication. The shift of treatment paradigm towards MART-treatment (Maintenance and Reliever Therapy) in asthma affects the treatment-related emissions. The carbon footprint of inhaled medication is also tied to the type of the device used. Today the most commonly used propellant-containing pressurised metered-dose inhalers (pMDIs) have a carbon footprint typically 20-40-fold higher than propellant-free dry powder inhalers (DPIs) and soft mist inhalers. METHODS: We analysed the carbon footprint of inhaled medications in Europe using published life cycle analyses of marketed inhalers and comprehensive 2020 European sales data. In addition, we give an estimate on treatment-related emissions of different treatment regimens on Global Initiative for Asthma (GINA) step 2. RESULTS: There is potential to reduce the carbon footprint of inhaled medications by 85% if DPIs are preferred over pMDIs. Emissions from pMDIs in the EU were estimated to be 4.0 megatons of carbon dioxide equivalent (MT CO2e) and this could be reduced to 0.6 MT CO2e if DPIs were used instead. In the treatment of moderate asthma with DPI, an as-needed combination of inhaled corticosteroid and long-acting beta-agonist in a single inhaler had a substantially lower annual carbon footprint (0.8 kg CO2e) than the more traditional maintenance therapy with an inhaled corticosteroid alone with as-needed short-acting beta-agonist (2.9 kg CO2e). DISCUSSION: There has been an urgent call for healthcare to reduce its carbon footprint for appropriate patients with asthma and chronic obstructive pulmonary disease (COPD), changing to non-propellant inhalers can reduce the carbon footprint of their treatment by almost 20-fold.

Effect of Vocalization on Human Aerosol Dynamics: Whispering Produces More Aerosols than Speaking.

OBJECTIVES: Sound pressure and exhaled flow have been identified as important factors associated with higher particle emissions. The aim of this study was to assess how different vocalizations affect the particle generation independently from other factors. DESIGN: Experimental study. METHODS: Thirty-three experienced singers repeated two different sentences in normal loudness and whispering. The first sentence consisted mainly of consonants like /k/ and /t/ as well as open vowels, while the second sentence also included the /s/ sound and contained primarily closed vowels. The particle emission was measured using condensation particle counter (CPC, 3775 TSI Inc.) and aerodynamic particle sizer (APS, 3321 TSI Inc.). The CPC measured particle number concentration for particles larger than 4 nm and mainly reflects the number of particles smaller than 0.5 µm since these particles dominate total number concentration. The APS measured particle size distribution and number concentration in the size range of 0.5-10 µm and data were divided into >1 µm and <1 µm particle size ranges. Generalized linear mixed-effects models were constructed to assess the factors affecting particle generation. RESULTS: Whispering produced more particles than speaking and sentence 1 produced more particles than sentence 2 while speaking. Sound pressure level had effect on particle production independently from vocalization. The effect of exhaled airflow was not statistically significant. CONCLUSIONS: Based on our results the type of vocalization has a significant effect on particle production independently from other factors such as sound pressure level.

Body Mass Index and the Risk of Adult-Onset Asthma: A Prospective Observational Study among 59,668 Middle-Aged Men and Women in Finland.

Introduction: Obesity, in addition to many other negative health consequences, affects pulmonary function and is a potential risk factor for asthma. Methods: We analyzed the association of body mass index (BMI) with incident asthma among 60,639 Finnish men and women aged 25 to 74 years who participated in a population-based chronic disease risk factor survey in 1972, 1977, 1982, 1987, 1992, 1997, 2002, 2007, or 2012. Data on lifestyle factors such as smoking and physical activity, as well as medical history, were obtained, and various physical measurements, including height and weight, were taken at baseline. Incident asthma events were ascertained from the National Social Insurance Institution's register data. The study cohorts were followed-up until the end of 2017 through registers. Results: During the follow-up, 4612 (14%) women and 2578 (9.3%) men developed asthma. The risk of asthma was analyzed in the following three BMI categories: <24.9 (reference category), 25-29.9 (overweight) and ≥30 kg/m2 (obesity). Hazard ratios (95% CI) were 1.34 (1.24-1.43) and 1.57 (1.44-1.71) in women and 1.25 (1.14-1.37) and 1.63 (1.44-1.83) in men. The observed association was independent of smoking, height and leisure-time physical activity. In women, 30.8% (19.2% in men) of the total asthma incidence was attributed to overweight and obesity. Conclusions: Overweight and obesity are important risk factors for asthma.

Salbutamol Easyhaler provides non-inferior relief of methacholine induced bronchoconstriction in comparison to Ventoline Evohaler with spacer: A randomized trial.

BACKGROUND: Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event. OBJECTIVE: We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed. METHODS: This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV1) were randomized to receive Salbutamol Easyhaler (2 × 200 µg), Ventoline Evohaler with spacer (4 × 100 µg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 µg) as a reliever. The treatment was repeated if FEV1 did not recover to at least -10 % of baseline. RESULTS: 180 participants (69 % females, mean age 46 yrs [range 18-80], FEV1%pred 89.5 [62-142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a -0.083 (95 % LCL -0.146) L FEV1 difference after the first dose and -0.032 (-0.071) L after the last dose. The differences in FEV1 between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were -0.163 (-0.225) L after the first and -0.092 (-0.131) L after the last dose. CONCLUSION: The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.

Successful Use of Easyhaler® Dry Powder Inhaler in Patients with Chronic Obstructive Pulmonary Disease; Analysis of Peak Inspiratory Flow from Three Clinical Trials.

INTRODUCTION: There is increasing pressure to use environmentally friendly dry powder inhalers (DPI) instead of pressurized metered-dose inhalers (pMDI). However, correct inhalation technique is needed for effective inhaler therapy, and there is persistent concern whether patients with chronic obstructive pulmonary disease (COPD) can generate sufficient inspiratory effort to use DPIs successfully. The aims of this study were to find clinical predictors for peak inspiratory flow rate (PIF) and to assess whether patients with COPD had difficulties in generating sufficient PIF with a high resistance DPI. METHODS: Pooled data of 246 patients with COPD from previous clinical trials was analyzed to find possible predictors of PIF via the DPI Easyhaler (PIFEH) and to assess the proportion of patients able to achieve an inhalation flow rate of 30 l/min, which is needed to use the Easyhaler successfully. RESULTS: The mean PIF was 56.9 l/min and 99% (243/246) of the study patients achieved a PIF ≥ 30 l/min. A low PIF was associated with female gender and lower forced expiratory volume in 1 s (FEV1), but the association was weak and a statistical model including both only accounted for 18% of the variation seen in PIFEH. CONCLUSIONS: Based on our results, impaired expiratory lung function or patient characteristics do not predict patients' ability to use DPIs in COPD; 99% of the patients generated sufficient PIFEH for successful dose delivery. Considering the targets for sustainability in health care, this should be addressed as DPIs are a potential option for most patients when choosing the right inhaler for the patient. TRIAL REGISTRATION: Two of three included trials were registered under numbers NCT04147572 and NCT01424137. Third trial preceded registration platforms and therefore, was not registered.

High inhaler resistance does not limit successful inspiratory maneuver among patients with asthma or COPD.

INTRODUCTION: There has been an active discussion on the sustainability of inhaler therapy in respiratory diseases, and it has cast a shadow on pMDIs which rely on propellant with high global warming potential (GWP). DPIs offer a lower GWP and effective alternative, but there has been concern whether all patients can generate sufficient inspiratory effort to disperse the drug. This review focuses on airflow resistance of DPIs and its clinical relevance. AREAS COVERED: For this narrative review, we searched the literature for studies comparing flow patterns with different devices. We also included a section on clinical trials comparing reliever administration with DPI, pMDI with spacer, and nebulizer during exacerbation. EXPERT OPINION: The evidence supports the efficacy of DPIs irrespective of respiratory condition or age of the patient even during acute exacerbations. Air flow resistance does not limit the use of DPIs and the patients were able to generate sufficient inspiratory flow rate with almost any device studied. None of 16 identified clinical trials comparing reliever administration via DPIs to other types of devices during exacerbation or bronchial challenge showed statistically significant difference between the device types in FEV1 recovery. DPIs performed as well as other types of inhaler devices even during asthma or COPD exacerbation.

The gut microbiome is a significant risk factor for future chronic lung disease.

BACKGROUND: The gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults. OBJECTIVE: We sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD). METHODS: Shallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status. RESULTS: A total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities. CONCLUSIONS: The gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors.

Contribution of smoking change to 45-year trend in prevalence of chronic bronchitis in Finland.

AIMS: Tobacco smoking has been identified as the most important risk factor of chronic bronchitis. The aim of this study was to assess the contribution of smoking to the trends in prevalence of chronic bronchitis among men and women in Finland. METHODS: For this purpose, we analysed questionnaires included in national FINRISK and FinHealth studies conducted between 1972 and 2017 in 5-year intervals. A total of 26,475 men and 28,684 women aged 30-59 years were included in the analysis. In addition to smoking, age and socioeconomic status were used as risk factors in the logistic regression model. RESULTS: Smoking in Finland has declined from 51% to 23% in men between 1972 and 2017. In women, it increased from 11% in 1972 to 23% in 2002, with a following decrease to 16% in 2017. The prevalence of chronic bronchitis has generally followed the trend of smoking. The population attributable risk was 60% in men and 49% in women. A decrease in chronic bronchitis was observed in male never-smokers. CONCLUSIONS: Smoking is currently declining in Finland in both men and women. As result, the prevalence of chronic bronchitis is declining and it is approaching baseline independent of smoking. The decrease in never-smokers has yet to be explained.

Inspiratory Flow Parameters Through Dry Powder Inhalers in Healthy Volunteers and Patients with Chronic Obstructive Pulmonary Disease (COPD): Device Resistance Does Not Limit Use in COPD.

INTRODUCTION: Achieving correct inhalation technique through an inhaler to ensure effective drug delivery is key to managing symptoms in patients with chronic obstructive pulmonary disease (COPD). However, many patients struggle to use their inhalers correctly, with the resultant reduction in therapeutic benefit. Consequently, appropriate inhaler choice is important to maximize clinical benefit. The primary objective of this study was to characterize inspiratory flow parameters across two Easyhaler® inhalers and the HandiHaler® inhaler in patients with COPD and healthy volunteers. METHODS: In this randomized, open-label, crossover study, subjects (100 patients with COPD; 100 healthy volunteers) were trained to perform inhalations of placebo powder via two variants of Easyhaler and placebo capsules via the HandiHaler inhalers. Subjects then performed three placebo inhalations through each inhaler in a random sequence. Inspiratory flow parameters were assessed, including peak inspiratory flow (PIF), for each inhaler. A parallel sub-study was conducted in patients with COPD from the main study to assess correct use of the inhalers, patient's preference, ability to learn to use the inhalers, and the feasibility of the In-Check Dial device to measure PIF values. RESULTS: Mean PIF rates and inspiratory volumes through the three inhalers were similar between patients with COPD and healthy volunteers, and all subjects achieved the 30 L/min PIF required for effective use of Easyhaler. Almost 70% of the 88 patients enrolled in the sub-study used the Easyhaler and HandiHaler inhalers without errors. The Easyhaler was preferred by 51% of patients, while 25% favored the HandiHaler. Teaching the use of both inhalers to almost 70% of patients was very easy. The In-Check Dial PIF values and those obtained via spirometry were strongly correlated (p<0.0001) for all three inhalers. CONCLUSION: The respiratory performance of patients with COPD does not appear to be a limiting factor in the use of Easyhaler.

Patients with asthma or chronic obstructive pulmonary disease (COPD) can generate sufficient inspiratory flows via Easyhaler® dry powder inhaler: a pooled analysis of two randomized controlled trials.

BACKGROUND: To evaluate whether patients of varying ages and lung function with asthma or those with chronic obstructive pulmonary disease (COPD) can achieve sufficient inspiratory flows for effective use of the fixed-dose combination of salmeterol-fluticasone propionate and budesonide-formoterol dispensed with the Easyhaler® (EH) device-metered, multi-dose dry powder inhaler (DPI). METHODS: A pooled analysis of two randomized, multicenter, crossover, open-label studies (NCT01424137; NCT009849061) was conducted to characterize inspiratory flow parameters across the EH, Seretide Diskus (DI) and Symbicort Turbuhaler (TH) inhalers in patients with asthma and/or COPD of varying severity. The primary endpoint was peak inspiratory flow (PIF) rate through the EH. RESULTS: The intent-to-treat population comprised 397 patients; 383 patients were included in the per-protocol (PP) population. The mean PIF (standard deviation) values through the EH in patients <18 and ≥18 years of age with asthma and in those with COPD, were similar: 61.4 (11.5), 69.7 (13.5), and 61.9 (13.2) L/min, respectively. These flow rates correspond to pressure drops of 5.05 (1.80), 6.52 (2.34) and 5.19 (2.07) kPa, respectively. In total, 380 (99.2%) of patients in the PP population were able to generate a PIF rate through the EH of ≥30 L/min, which is required to enable consistent dose delivery from the DPI; there was a moderate direct association between age and PIF in younger patients with asthma, but this was inverse and less apparent in adult patients with asthma and/or those with COPD. Height and weight were also moderately correlated with PIF. Stronger associations with PIF were observed for some lung function parameters, particularly native PIF and forced inspiratory vital capacity. CONCLUSIONS: Over 99% of patients with asthma and/or COPD were able to inhale through the EH with an adequate PIF rate, irrespective of age, or severity of airway obstruction. This confirms that patients with asthma and/or COPD can achieve inspiratory flows via the EH DPI that are sufficient for its effective use.

Patient Inspiratory Maneuver Performance; Peak Lungpower, Acceleration and Volume.

Background: Use of drug delivery devices between nebulizers, dry powder inhalers (DPIs), or metered dose inhalers (MDIs), for treating patients with asthma and chronic obstructive pulmonary disease (COPD), is based on patients' capability of coordinating the inhalation maneuver and achieving sufficient airflow. There are limited data available with regard to how patients meet the requirements of successful inhalation performance, and how the concept of inspiratory lungpower could be applied. The aim of this work was to study the patient inspiratory airflow profile performance in large data sets. We analyzed how the Kamin-Haidl inhalation criteria were met by patients with DPIs such as Easyhaler for combination therapy (EH-combi), Easyhaler for monotherapy (EH-mono), Diskus, and Turbuhaler (TH), and applied peak lungpower instead of peak inspiratory flow rate as an indicator of patient performance. Materials and Methods: Data sets gathered in two previous studies for DPIs, that is, EH-combi, EH-mono, Diskus, and TH, were used to analyze how inspiratory lungpower representing inspiratory muscle power, flow acceleration, and volume after peak met the inhalation criteria. The measured patient airflow profiles through inhalers were assessed for patients with asthma or COPD. Results: Based on the Kamin-Haidl inhalation criteria, successful inhalation requirements were met with EH-combi in 96.1% and with EH-mono in 92.6% of patients. The success rates were 89.5% and 84.6% with Diskus and TH, respectively, (p < 0.0001 between devices). In patients with asthma or COPD, the mean lungpower was 7.51 and 6.15 W for EH-combi, 8.79 and 6.88 W for EH-mono, 7.18 and 4.36 W for Diskus, and 9.65 and 6.86 W for TH, respectively, when patients followed the manufacturer's written instructions. Conclusions: Lungpower applied to the Kamin-Haidl inhalation criteria concept could be an applicable method for reviewing patient performance for different DPIs despite DPIs' characteristic differences in airflow resistance. In light of these results, DPIs provide a feasible treatment option for a large majority of respiratory patients.

Label-free plasma proteomics identifies haptoglobin-related protein as candidate marker of idiopathic pulmonary fibrosis and dysregulation of complement and oxidative pathways.

Idiopathic pulmonary fibrosis (IPF) is a lung parenchymal disease of unknown cause usually occurring in older adults. It is a chronic and progressive condition with poor prognosis and diagnosis is largely clinical. Currently, there exist few biomarkers that can predict patient outcome or response to therapies. Together with lack of markers, the need for novel markers for the detection and monitoring of IPF, is paramount. We have performed label-free plasma proteomics of thirty six individuals, 17 of which had confirmed IPF. Proteomics data was analyzed by volcano plot, hierarchical clustering, Partial-least square discriminant analysis (PLS-DA) and Ingenuity pathway analysis. Univariate and multivariate statistical analysis overlap identified haptoglobin-related protein as a possible marker of IPF when compared to control samples (Area under the curve 0.851, ROC-analysis). LXR/RXR activation and complement activation pathways were enriched in t-test significant proteins and oxidative regulators, complement proteins and protease inhibitors were enriched in PLS-DA significant proteins. Our pilot study points towards aberrations in complement activation and oxidative damage in IPF patients and provides haptoglobin-related protein as a new candidate biomarker of IPF.

Pirfenidone decreases mesothelioma cell proliferation and migration via inhibition of ERK and AKT and regulates mesothelioma tumor microenvironment in vivo.

Malignant mesothelioma is an aggressive cancer with poor prognosis. It is characterized by prominent extracellular matrix, mesenchymal tumor cell phenotypes and chemoresistance. In this study, the ability of pirfenidone to alter mesothelioma cell proliferation and migration as well as mesothelioma tumor microenvironment was evaluated. Pirfenidone is an anti-fibrotic drug used in the treatment of idiopathic pulmonary fibrosis and has also anti-proliferative activities. Mesothelioma cell proliferation was decreased by pirfenidone alone or in combination with cisplatin. Pirfenidone also decreased significantly Transwell migration/invasion and 3D collagen invasion. This was associated with increased BMP pathway activity, decreased GREM1 expression and downregulation of MAPK/ERK and AKT/mTOR signaling. The canonical Smad-mediated TGF-ß signaling was not affected by pirfenidone. However, pirfenidone blocked TGF-ß induced upregulation of ERK and AKT pathways. Treatment of mice harboring mesothelioma xenografts with pirfenidone alone did not reduce tumor proliferation in vivo. However, pirfenidone modified the tumor microenvironment by reducing the expression of extracellular matrix associated genes. In addition, GREM1 expression was downregulated by pirfenidone in vivo. By reducing two major upregulated pathways in mesothelioma and by targeting tumor cells and the microenvironment pirfenidone may present a novel anti-fibrotic and anti-cancer adjuvant therapy for mesothelioma.

Pulmonary administration of a dry powder formulation of the antifibrotic drug tilorone reduces silica-induced lung fibrosis in mice.

The aim of this work was to study the antifibrotic effect of pulmonary administration of tilorone to lung fibrosis. L-leucine coated tilorone particles were prepared and their aerosolization properties were analyzed using two dry powder inhalers (Easyhaler and Twister). In addition, the biological activity and cell monolayer permeation was tested. The antifibrotic effect of tilorone delivered by oropharyngeal aspiration was studied in vivo using a silica-induced model of pulmonary fibrosis in mice in a preventive setting. When delivered from the Easyhaler in an inhalation simulator, the emitted dose and fine particle fraction were independent from the pressure applied and showed dose repeatability. However, with Twister the aerosolization was pressure-dependent indicating poor compatibility between the device and the formulation. The formulation showed more consistent permeation through a differentiated Calu-3 cell monolayer compared to pristine tilorone. Tilorone decreased the histological fibrosis score in vivo in systemic and local administration, but only systemic administration decreased the mRNA expression of type I collagen. The difference was hypothesized to result from 40-fold higher drug concentration in tissue samples in the systemic administration group. These results show that tilorone can be formulated as inhalable dry powder and has potential as an oral and inhalable antifibrotic drug.

Aerosolization, Drug Permeation and Cellular Interaction of Dry Powder Pulmonary Formulations of Corticosteroids with Hydroxypropyl-ß-Cyclodextrin as a Solubilizer.

PURPOSE: The purpose of this study was to assess the feasibility of hydroxypropyl-ß-cyclodextrin as a solubilizer for the corticosteroids prednisolone and fludrocortisone acetate in dry powder inhalation formulations. METHODS: The dry particles were simultaneously produced and coated with nanosized L-leucine crystals using an aerosol flow reactor method. The aerosolization performances of carrier-free powders were studied using Easyhaler® and Twister™ at 2 and 4 kPa pressure drops over the inhalers. Drug permeation properties of the formulations were tested across a Calu-3 cell monolayer. Toxicity and reactive oxygen species induction were tested against Calu-3 and A549 cell lines. RESULTS: The hydroxypropyl-ß-cyclodextrin in the powders promoted the dissolution of fludrocortisone the most, followed by that of prednisolone. Fine particle fractions were 52-70% from emitted doses which showed good repeatability with a coefficient variation of 0.9-0.17. In addition, hydroxypropyl-ß-cyclodextrin enhanced the permeation of the corticosteroids. The powders showed no statistically significant toxicity nor reactive oxygen species induction in the tested cell lines. CONCLUSIONS: This study demonstrated the preparation and function of fine powder formulations which combine improved dissolution of poorly soluble drugs with good aerosolization performance. These results are expected to promote particle engineering as a way to develop new types of therapeutic pulmonary powders.

Drug permeation and cellular interaction of amino acid-coated drug combination powders for pulmonary delivery.

The effect of three amino acid coatings (L-leucine, L-valine and L-phenylalanine) on particle integrity, aerosolization properties, cellular interaction, cytocompatibility, and drug permeation properties of drug combination powder particles (beclomethasone dipropionate and salbutamol sulphate) for dry powder inhalation (DPI) was investigated. Particles with crystalline L-leucine coating resulted in intact separated particles, with crystalline L-valine coating in slightly sintered particles and with amorphous L-phenylalanine coating in strongly fused particles. The permeation of beclomethasone dipropionate across a Calu-3 differentiated cell monolayer was increased when compared with its physical mixture. Drug crystal formation was also observed on the Calu-3 cell monolayer. The L-leucine coated particles were further investigated for cytocompatibility in three human pulmonary (Calu-3, A549 and BEAS-2B) and one human macrophage (THP-1) cell lines, where they showed excellent tolerability. The l-leucine coated particles were also examined for their ability to elicit reactive oxygen species in pulmonary BEAS-2B and macrophage THP-1 cell lines. The study showed the influence of the amino acid coatings for particle formation and performance and their feasibility for combination therapy for pulmonary delivery.

Polypeptide-based aerosol nanoparticles: self-assembly and control of conformation by solvent and thermal annealing.

Nanoconfined self-assemblies within aerosol nanoparticles and control of the secondary structures are shown here upon ionically complexing poly(L-lysine) (PLL) with dodecylbenzenesulfonic acid (DBSA) surfactant and using solvents chloroform, 1-propanol, or dimethylformamide. Different solvent volatilities and drying temperatures allowed tuning the kinetics of morphology formation. The supramolecular self-assembly and morphology were studied using cryo-TEM and SEM, and the secondary structures, using FT-IR. Highly volatile chloroform led to the major fraction of α-helical conformation of PLL(DBSA), whereas less volatile solvents or higher drying temperatures led to the increasing fraction of ß-sheets. Added drugs budesonide and ketoprofen prevented ß-sheet formation and studied PLL(DBSA)-drug nanoparticles were in the α-helical conformation. Preliminary studies showed that ketoprofen released with a slower rate than budesonide which was hypothesized to result from different localization of drugs within the PLL(DBSA) nanoparticles. These results instruct to prepare polypeptide aerosol nanoparticles with internal self-assembled structures and to control the secondary structures by aerosol solvent annealing, which we foresee to be useful, e.g., toward controlling the release of poorly soluble drug molecules.